<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kasela, Silva</style></author><author><style face="normal" font="default" size="100%">Ortega, Victor E</style></author><author><style face="normal" font="default" size="100%">Martorella, Molly</style></author><author><style face="normal" font="default" size="100%">Garudadri, Suresh</style></author><author><style face="normal" font="default" size="100%">Nguyen, Jenna</style></author><author><style face="normal" font="default" size="100%">Ampleford, Elizabeth</style></author><author><style face="normal" font="default" size="100%">Pasanen, Anu</style></author><author><style face="normal" font="default" size="100%">Nerella, Srilaxmi</style></author><author><style face="normal" font="default" size="100%">Buschur, Kristina L</style></author><author><style face="normal" font="default" size="100%">Barjaktarevic, Igor Z</style></author><author><style face="normal" font="default" size="100%">Barr, R Graham</style></author><author><style face="normal" font="default" size="100%">Bleecker, Eugene R</style></author><author><style face="normal" font="default" size="100%">Bowler, Russell P</style></author><author><style face="normal" font="default" size="100%">Comellas, Alejandro P</style></author><author><style face="normal" font="default" size="100%">Cooper, Christopher B</style></author><author><style face="normal" font="default" size="100%">Couper, David J</style></author><author><style face="normal" font="default" size="100%">Criner, Gerard J</style></author><author><style face="normal" font="default" size="100%">Curtis, Jeffrey L</style></author><author><style face="normal" font="default" size="100%">Han, MeiLan K</style></author><author><style face="normal" font="default" size="100%">Hansel, Nadia N</style></author><author><style face="normal" font="default" size="100%">Hoffman, Eric A</style></author><author><style face="normal" font="default" size="100%">Kaner, Robert J</style></author><author><style face="normal" font="default" size="100%">Krishnan, Jerry A</style></author><author><style face="normal" font="default" size="100%">Martinez, Fernando J</style></author><author><style face="normal" font="default" size="100%">McDonald, Merry-Lynn N</style></author><author><style face="normal" font="default" size="100%">Meyers, Deborah A</style></author><author><style face="normal" font="default" size="100%">Paine, Robert</style></author><author><style face="normal" font="default" size="100%">Peters, Stephen P</style></author><author><style face="normal" font="default" size="100%">Castro, Mario</style></author><author><style face="normal" font="default" size="100%">Denlinger, Loren C</style></author><author><style face="normal" font="default" size="100%">Erzurum, Serpil C</style></author><author><style face="normal" font="default" size="100%">Fahy, John V</style></author><author><style face="normal" font="default" size="100%">Israel, Elliot</style></author><author><style face="normal" font="default" size="100%">Jarjour, Nizar N</style></author><author><style face="normal" font="default" size="100%">Levy, Bruce D</style></author><author><style face="normal" font="default" size="100%">Li, Xingnan</style></author><author><style face="normal" font="default" size="100%">Moore, Wendy C</style></author><author><style face="normal" font="default" size="100%">Wenzel, Sally E</style></author><author><style face="normal" font="default" size="100%">Zein, Joe</style></author><author><style face="normal" font="default" size="100%">Langelier, Charles</style></author><author><style face="normal" font="default" size="100%">Woodruff, Prescott G</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author><author><style face="normal" font="default" size="100%">Christenson, Stephanie A</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)</style></author><author><style face="normal" font="default" size="100%">NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium.</style></title><secondary-title><style face="normal" font="default" size="100%">Genome Med</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Genome Med</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged, 80 and over</style></keyword><keyword><style  face="normal" font="default" size="100%">Angiotensin-Converting Enzyme 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Asthma</style></keyword><keyword><style  face="normal" font="default" size="100%">Bronchi</style></keyword><keyword><style  face="normal" font="default" size="100%">Cardiovascular Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">COVID-19</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Obesity</style></keyword><keyword><style  face="normal" font="default" size="100%">Pulmonary Disease, Chronic Obstructive</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Respiratory Mucosa</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">SARS-CoV-2</style></keyword><keyword><style  face="normal" font="default" size="100%">Smoking</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021 04 21</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">13</style></volume><pages><style face="normal" font="default" size="100%">66</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33883027?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ilumäe, Anne-Mai</style></author><author><style face="normal" font="default" size="100%">Post, Helen</style></author><author><style face="normal" font="default" size="100%">Flores, Rodrigo</style></author><author><style face="normal" font="default" size="100%">Karmin, Monika</style></author><author><style face="normal" font="default" size="100%">Sahakyan, Hovhannes</style></author><author><style face="normal" font="default" size="100%">Mondal, Mayukh</style></author><author><style face="normal" font="default" size="100%">Montinaro, Francesco</style></author><author><style face="normal" font="default" size="100%">Saag, Lauri</style></author><author><style face="normal" font="default" size="100%">Bormans, Concetta</style></author><author><style face="normal" font="default" size="100%">Sanchez, Luisa Fernanda</style></author><author><style face="normal" font="default" size="100%">Ameur, Adam</style></author><author><style face="normal" font="default" size="100%">Gyllensten, Ulf</style></author><author><style face="normal" font="default" size="100%">Kals, Mart</style></author><author><style face="normal" font="default" size="100%">Mägi, Reedik</style></author><author><style face="normal" font="default" size="100%">Pagani, Luca</style></author><author><style face="normal" font="default" size="100%">Behar, Doron M</style></author><author><style face="normal" font="default" size="100%">Rootsi, Siiri</style></author><author><style face="normal" font="default" size="100%">Villems, Richard</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Phylogenetic history of patrilineages rare in northern and eastern Europe from large-scale re-sequencing of human Y-chromosomes.</style></title><secondary-title><style face="normal" font="default" size="100%">Eur J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Eur J Hum Genet</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021 May 07</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The most frequent Y-chromosomal (chrY) haplogroups in northern and eastern Europe (NEE) are well-known and thoroughly characterised. Yet a considerable number of men in every population carry rare paternal lineages with estimated frequencies around 5%. So far, limited sample-sizes and insufficient resolution of genotyping have obstructed a truly comprehensive look into the variety of rare paternal lineages segregating within populations and potential signals of population history that such lineages might convey. Here we harness the power of massive re-sequencing of human Y chromosomes to identify previously unknown population-specific clusters among rare paternal lineages in NEE. We construct dated phylogenies for haplogroups E2-M215, J2-M172, G-M201 and Q-M242 on the basis of 421 (of them 282 novel) high-coverage chrY sequences collected from large-scale databases focusing on populations of NEE. Within these otherwise rare haplogroups we disclose lineages that began to radiate ~1-3 thousand years ago in Estonia and Sweden and reveal male phylogenetic patterns testifying of comparatively recent local demographic expansions. Conversely, haplogroup Q lineages bear evidence of ancient Siberian influence lingering in the modern paternal gene pool of northern Europe. We assess the possible direction of influx of ancestral carriers for some of these male lineages. In addition, we demonstrate the congruency of paternal haplogroup composition of our dataset with two independent population-based cohorts from Estonia and Sweden.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33958743?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Somineni, Hari K</style></author><author><style face="normal" font="default" size="100%">Nagpal, Sini</style></author><author><style face="normal" font="default" size="100%">Venkateswaran, Suresh</style></author><author><style face="normal" font="default" size="100%">Cutler, David J</style></author><author><style face="normal" font="default" size="100%">Okou, David T</style></author><author><style face="normal" font="default" size="100%">Haritunians, Talin</style></author><author><style face="normal" font="default" size="100%">Simpson, Claire L</style></author><author><style face="normal" font="default" size="100%">Begum, Ferdouse</style></author><author><style face="normal" font="default" size="100%">Datta, Lisa W</style></author><author><style face="normal" font="default" size="100%">Quiros, Antonio J</style></author><author><style face="normal" font="default" size="100%">Seminerio, Jenifer</style></author><author><style face="normal" font="default" size="100%">Mengesha, Emebet</style></author><author><style face="normal" font="default" size="100%">Alexander, Jonathan S</style></author><author><style face="normal" font="default" size="100%">Baldassano, Robert N</style></author><author><style face="normal" font="default" size="100%">Dudley-Brown, Sharon</style></author><author><style face="normal" font="default" size="100%">Cross, Raymond K</style></author><author><style face="normal" font="default" size="100%">Dassopoulos, Themistocles</style></author><author><style face="normal" font="default" size="100%">Denson, Lee A</style></author><author><style face="normal" font="default" size="100%">Dhere, Tanvi A</style></author><author><style face="normal" font="default" size="100%">Iskandar, Heba</style></author><author><style face="normal" font="default" size="100%">Dryden, Gerald W</style></author><author><style face="normal" font="default" size="100%">Hou, Jason K</style></author><author><style face="normal" font="default" size="100%">Hussain, Sunny Z</style></author><author><style face="normal" font="default" size="100%">Hyams, Jeffrey S</style></author><author><style face="normal" font="default" size="100%">Isaacs, Kim L</style></author><author><style face="normal" font="default" size="100%">Kader, Howard</style></author><author><style face="normal" font="default" size="100%">Kappelman, Michael D</style></author><author><style face="normal" font="default" size="100%">Katz, Jeffry</style></author><author><style face="normal" font="default" size="100%">Kellermayer, Richard</style></author><author><style face="normal" font="default" size="100%">Kuemmerle, John F</style></author><author><style face="normal" font="default" size="100%">Lazarev, Mark</style></author><author><style face="normal" font="default" size="100%">Li, Ellen</style></author><author><style face="normal" font="default" size="100%">Mannon, Peter</style></author><author><style face="normal" font="default" size="100%">Moulton, Dedrick E</style></author><author><style face="normal" font="default" size="100%">Newberry, Rodney D</style></author><author><style face="normal" font="default" size="100%">Patel, Ashish S</style></author><author><style face="normal" font="default" size="100%">Pekow, Joel</style></author><author><style face="normal" font="default" size="100%">Saeed, Shehzad A</style></author><author><style face="normal" font="default" size="100%">Valentine, John F</style></author><author><style face="normal" font="default" size="100%">Wang, Ming-Hsi</style></author><author><style face="normal" font="default" size="100%">McCauley, Jacob L</style></author><author><style face="normal" font="default" size="100%">Abreu, Maria T</style></author><author><style face="normal" font="default" size="100%">Jester, Traci</style></author><author><style face="normal" font="default" size="100%">Molle-Rios, Zarela</style></author><author><style face="normal" font="default" size="100%">Palle, Sirish</style></author><author><style face="normal" font="default" size="100%">Scherl, Ellen J</style></author><author><style face="normal" font="default" size="100%">Kwon, John</style></author><author><style face="normal" font="default" size="100%">Rioux, John D</style></author><author><style face="normal" font="default" size="100%">Duerr, Richard H</style></author><author><style face="normal" font="default" size="100%">Silverberg, Mark S</style></author><author><style face="normal" font="default" size="100%">Zwick, Michael E</style></author><author><style face="normal" font="default" size="100%">Stevens, Christine</style></author><author><style face="normal" font="default" size="100%">Daly, Mark J</style></author><author><style face="normal" font="default" size="100%">Cho, Judy H</style></author><author><style face="normal" font="default" size="100%">Gibson, Greg</style></author><author><style face="normal" font="default" size="100%">McGovern, Dermot P B</style></author><author><style face="normal" font="default" size="100%">Brant, Steven R</style></author><author><style face="normal" font="default" size="100%">Kugathasan, Subra</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Whole-genome sequencing of African Americans implicates differential genetic architecture in inflammatory bowel disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">African Americans</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged, 80 and over</style></keyword><keyword><style  face="normal" font="default" size="100%">Calbindin 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Colitis, Ulcerative</style></keyword><keyword><style  face="normal" font="default" size="100%">Crohn Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">European Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammatory Bowel Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Multifactorial Inheritance</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Receptors, Prostaglandin E, EP4 Subtype</style></keyword><keyword><style  face="normal" font="default" size="100%">Whole Genome Sequencing</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021 03 04</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">108</style></volume><pages><style face="normal" font="default" size="100%">431-445</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 SNPs corresponding to one of four independent associations at the locus in European ancestry individuals but with an elevated odds ratio for Crohn disease in African Americans. A rare variant aggregate analysis implicates Ca-binding neuro-immunomodulator CALB2 in ulcerative colitis. Highly significant overall overlap of common variant risk for inflammatory bowel disease susceptibility between individuals with African and European ancestries was observed, with 41 of 241 previously known lead variants replicated and overall correlations in effect sizes of 0.68 for combined inflammatory bowel disease. Nevertheless, subtle differences influence the performance of polygenic risk scores, and we show that ancestry-appropriate weights significantly improve polygenic prediction in the highest percentiles of risk. The median amount of variance explained per locus remains the same in African and European cohorts, providing evidence for compensation of effect sizes as allele frequencies diverge, as expected under a highly polygenic model of disease.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33600772?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Kim-Hellmuth, Sarah</style></author><author><style face="normal" font="default" size="100%">Aguet, François</style></author><author><style face="normal" font="default" size="100%">Oliva, Meritxell</style></author><author><style face="normal" font="default" size="100%">Muñoz-Aguirre, Manuel</style></author><author><style face="normal" font="default" size="100%">Kasela, Silva</style></author><author><style face="normal" font="default" size="100%">Wucher, Valentin</style></author><author><style face="normal" font="default" size="100%">Castel, Stephane E</style></author><author><style face="normal" font="default" size="100%">Hamel, Andrew R</style></author><author><style face="normal" font="default" size="100%">Viñuela, Ana</style></author><author><style face="normal" font="default" size="100%">Roberts, Amy L</style></author><author><style face="normal" font="default" size="100%">Mangul, Serghei</style></author><author><style face="normal" font="default" size="100%">Wen, Xiaoquan</style></author><author><style face="normal" font="default" size="100%">Wang, Gao</style></author><author><style face="normal" font="default" size="100%">Barbeira, Alvaro N</style></author><author><style face="normal" font="default" size="100%">Garrido-Martín, Diego</style></author><author><style face="normal" font="default" size="100%">Nadel, Brian B</style></author><author><style face="normal" font="default" size="100%">Zou, Yuxin</style></author><author><style face="normal" font="default" size="100%">Bonazzola, Rodrigo</style></author><author><style face="normal" font="default" size="100%">Quan, Jie</style></author><author><style face="normal" font="default" size="100%">Brown, Andrew</style></author><author><style face="normal" font="default" size="100%">Martinez-Perez, Angel</style></author><author><style face="normal" font="default" size="100%">Soria, José Manuel</style></author><author><style face="normal" font="default" size="100%">Getz, Gad</style></author><author><style face="normal" font="default" size="100%">Dermitzakis, Emmanouil T</style></author><author><style face="normal" font="default" size="100%">Small, Kerrin S</style></author><author><style face="normal" font="default" size="100%">Stephens, Matthew</style></author><author><style face="normal" font="default" size="100%">Xi, Hualin S</style></author><author><style face="normal" font="default" size="100%">Im, Hae Kyung</style></author><author><style face="normal" font="default" size="100%">Guigo, Roderic</style></author><author><style face="normal" font="default" size="100%">Segrè, Ayellet V</style></author><author><style face="normal" font="default" size="100%">Stranger, Barbara E</style></author><author><style face="normal" font="default" size="100%">Ardlie, Kristin G</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">GTEx Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Cell type-specific genetic regulation of gene expression across human tissues.</style></title><secondary-title><style face="normal" font="default" size="100%">Science</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Science</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Organ Specificity</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">RNA, Long Noncoding</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 09 11</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">369</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6509</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32913075?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Oliva, Meritxell</style></author><author><style face="normal" font="default" size="100%">Muñoz-Aguirre, Manuel</style></author><author><style face="normal" font="default" size="100%">Kim-Hellmuth, Sarah</style></author><author><style face="normal" font="default" size="100%">Wucher, Valentin</style></author><author><style face="normal" font="default" size="100%">Gewirtz, Ariel D H</style></author><author><style face="normal" font="default" size="100%">Cotter, Daniel J</style></author><author><style face="normal" font="default" size="100%">Parsana, Princy</style></author><author><style face="normal" font="default" size="100%">Kasela, Silva</style></author><author><style face="normal" font="default" size="100%">Balliu, Brunilda</style></author><author><style face="normal" font="default" size="100%">Viñuela, Ana</style></author><author><style face="normal" font="default" size="100%">Castel, Stephane E</style></author><author><style face="normal" font="default" size="100%">Mohammadi, Pejman</style></author><author><style face="normal" font="default" size="100%">Aguet, François</style></author><author><style face="normal" font="default" size="100%">Zou, Yuxin</style></author><author><style face="normal" font="default" size="100%">Khramtsova, Ekaterina A</style></author><author><style face="normal" font="default" size="100%">Skol, Andrew D</style></author><author><style face="normal" font="default" size="100%">Garrido-Martín, Diego</style></author><author><style face="normal" font="default" size="100%">Reverter, Ferran</style></author><author><style face="normal" font="default" size="100%">Brown, Andrew</style></author><author><style face="normal" font="default" size="100%">Evans, Patrick</style></author><author><style face="normal" font="default" size="100%">Gamazon, Eric R</style></author><author><style face="normal" font="default" size="100%">Payne, Anthony</style></author><author><style face="normal" font="default" size="100%">Bonazzola, Rodrigo</style></author><author><style face="normal" font="default" size="100%">Barbeira, Alvaro N</style></author><author><style face="normal" font="default" size="100%">Hamel, Andrew R</style></author><author><style face="normal" font="default" size="100%">Martinez-Perez, Angel</style></author><author><style face="normal" font="default" size="100%">Soria, José Manuel</style></author><author><style face="normal" font="default" size="100%">Pierce, Brandon L</style></author><author><style face="normal" font="default" size="100%">Stephens, Matthew</style></author><author><style face="normal" font="default" size="100%">Eskin, Eleazar</style></author><author><style face="normal" font="default" size="100%">Dermitzakis, Emmanouil T</style></author><author><style face="normal" font="default" size="100%">Segrè, Ayellet V</style></author><author><style face="normal" font="default" size="100%">Im, Hae Kyung</style></author><author><style face="normal" font="default" size="100%">Engelhardt, Barbara E</style></author><author><style face="normal" font="default" size="100%">Ardlie, Kristin G</style></author><author><style face="normal" font="default" size="100%">Montgomery, Stephen B</style></author><author><style face="normal" font="default" size="100%">Battle, Alexis J</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author><author><style face="normal" font="default" size="100%">Guigo, Roderic</style></author><author><style face="normal" font="default" size="100%">Stranger, Barbara E</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">GTEx Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">The impact of sex on gene expression across human tissues.</style></title><secondary-title><style face="normal" font="default" size="100%">Science</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Science</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Chromosomes, Human, X</style></keyword><keyword><style  face="normal" font="default" size="100%">Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Epigenesis, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Organ Specificity</style></keyword><keyword><style  face="normal" font="default" size="100%">Promoter Regions, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword><keyword><style  face="normal" font="default" size="100%">Sex Characteristics</style></keyword><keyword><style  face="normal" font="default" size="100%">Sex Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 09 11</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">369</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6509</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32913072?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Bick, Alexander G</style></author><author><style face="normal" font="default" size="100%">Weinstock, Joshua S</style></author><author><style face="normal" font="default" size="100%">Nandakumar, Satish K</style></author><author><style face="normal" font="default" size="100%">Fulco, Charles P</style></author><author><style face="normal" font="default" size="100%">Bao, Erik L</style></author><author><style face="normal" font="default" size="100%">Zekavat, Seyedeh M</style></author><author><style face="normal" font="default" size="100%">Szeto, Mindy D</style></author><author><style face="normal" font="default" size="100%">Liao, Xiaotian</style></author><author><style face="normal" font="default" size="100%">Leventhal, Matthew J</style></author><author><style face="normal" font="default" size="100%">Nasser, Joseph</style></author><author><style face="normal" font="default" size="100%">Chang, Kyle</style></author><author><style face="normal" font="default" size="100%">Laurie, Cecelia</style></author><author><style face="normal" font="default" size="100%">Burugula, Bala Bharathi</style></author><author><style face="normal" font="default" size="100%">Gibson, Christopher J</style></author><author><style face="normal" font="default" size="100%">Lin, Amy E</style></author><author><style face="normal" font="default" size="100%">Taub, Margaret A</style></author><author><style face="normal" font="default" size="100%">Aguet, François</style></author><author><style face="normal" font="default" size="100%">Ardlie, Kristin</style></author><author><style face="normal" font="default" size="100%">Mitchell, Braxton D</style></author><author><style face="normal" font="default" size="100%">Barnes, Kathleen C</style></author><author><style face="normal" font="default" size="100%">Moscati, Arden</style></author><author><style face="normal" font="default" size="100%">Fornage, Myriam</style></author><author><style face="normal" font="default" size="100%">Redline, Susan</style></author><author><style face="normal" font="default" size="100%">Psaty, Bruce M</style></author><author><style face="normal" font="default" size="100%">Silverman, Edwin K</style></author><author><style face="normal" font="default" size="100%">Weiss, Scott T</style></author><author><style face="normal" font="default" size="100%">Palmer, Nicholette D</style></author><author><style face="normal" font="default" size="100%">Vasan, Ramachandran S</style></author><author><style face="normal" font="default" size="100%">Burchard, Esteban G</style></author><author><style face="normal" font="default" size="100%">Kardia, Sharon L R</style></author><author><style face="normal" font="default" size="100%">He, Jiang</style></author><author><style face="normal" font="default" size="100%">Kaplan, Robert C</style></author><author><style face="normal" font="default" size="100%">Smith, Nicholas L</style></author><author><style face="normal" font="default" size="100%">Arnett, Donna K</style></author><author><style face="normal" font="default" size="100%">Schwartz, David A</style></author><author><style face="normal" font="default" size="100%">Correa, Adolfo</style></author><author><style face="normal" font="default" size="100%">de Andrade, Mariza</style></author><author><style face="normal" font="default" size="100%">Guo, Xiuqing</style></author><author><style face="normal" font="default" size="100%">Konkle, Barbara A</style></author><author><style face="normal" font="default" size="100%">Custer, Brian</style></author><author><style face="normal" font="default" size="100%">Peralta, Juan M</style></author><author><style face="normal" font="default" size="100%">Gui, Hongsheng</style></author><author><style face="normal" font="default" size="100%">Meyers, Deborah A</style></author><author><style face="normal" font="default" size="100%">McGarvey, Stephen T</style></author><author><style face="normal" font="default" size="100%">Chen, Ida Yii-Der</style></author><author><style face="normal" font="default" size="100%">Shoemaker, M Benjamin</style></author><author><style face="normal" font="default" size="100%">Peyser, Patricia A</style></author><author><style face="normal" font="default" size="100%">Broome, Jai G</style></author><author><style face="normal" font="default" size="100%">Gogarten, Stephanie M</style></author><author><style face="normal" font="default" size="100%">Wang, Fei Fei</style></author><author><style face="normal" font="default" size="100%">Wong, Quenna</style></author><author><style face="normal" font="default" size="100%">Montasser, May E</style></author><author><style face="normal" font="default" size="100%">Daya, Michelle</style></author><author><style face="normal" font="default" size="100%">Kenny, Eimear E</style></author><author><style face="normal" font="default" size="100%">North, Kari E</style></author><author><style face="normal" font="default" size="100%">Launer, Lenore J</style></author><author><style face="normal" font="default" size="100%">Cade, Brian E</style></author><author><style face="normal" font="default" size="100%">Bis, Joshua C</style></author><author><style face="normal" font="default" size="100%">Cho, Michael H</style></author><author><style face="normal" font="default" size="100%">Lasky-Su, Jessica</style></author><author><style face="normal" font="default" size="100%">Bowden, Donald W</style></author><author><style face="normal" font="default" size="100%">Cupples, L Adrienne</style></author><author><style face="normal" font="default" size="100%">Mak, Angel C Y</style></author><author><style face="normal" font="default" size="100%">Becker, Lewis C</style></author><author><style face="normal" font="default" size="100%">Smith, Jennifer A</style></author><author><style face="normal" font="default" size="100%">Kelly, Tanika N</style></author><author><style face="normal" font="default" size="100%">Aslibekyan, Stella</style></author><author><style face="normal" font="default" size="100%">Heckbert, Susan R</style></author><author><style face="normal" font="default" size="100%">Tiwari, Hemant K</style></author><author><style face="normal" font="default" size="100%">Yang, Ivana V</style></author><author><style face="normal" font="default" size="100%">Heit, John A</style></author><author><style face="normal" font="default" size="100%">Lubitz, Steven A</style></author><author><style face="normal" font="default" size="100%">Johnsen, Jill M</style></author><author><style face="normal" font="default" size="100%">Curran, Joanne E</style></author><author><style face="normal" font="default" size="100%">Wenzel, Sally E</style></author><author><style face="normal" font="default" size="100%">Weeks, Daniel E</style></author><author><style face="normal" font="default" size="100%">Rao, Dabeeru C</style></author><author><style face="normal" font="default" size="100%">Darbar, Dawood</style></author><author><style face="normal" font="default" size="100%">Moon, Jee-Young</style></author><author><style face="normal" font="default" size="100%">Tracy, Russell P</style></author><author><style face="normal" font="default" size="100%">Buth, Erin J</style></author><author><style face="normal" font="default" size="100%">Rafaels, Nicholas</style></author><author><style face="normal" font="default" size="100%">Loos, Ruth J F</style></author><author><style face="normal" font="default" size="100%">Durda, Peter</style></author><author><style face="normal" font="default" size="100%">Liu, Yongmei</style></author><author><style face="normal" font="default" size="100%">Hou, Lifang</style></author><author><style face="normal" font="default" size="100%">Lee, Jiwon</style></author><author><style face="normal" font="default" size="100%">Kachroo, Priyadarshini</style></author><author><style face="normal" font="default" size="100%">Freedman, Barry I</style></author><author><style face="normal" font="default" size="100%">Levy, Daniel</style></author><author><style face="normal" font="default" size="100%">Bielak, Lawrence F</style></author><author><style face="normal" font="default" size="100%">Hixson, James E</style></author><author><style face="normal" font="default" size="100%">Floyd, James S</style></author><author><style face="normal" font="default" size="100%">Whitsel, Eric A</style></author><author><style face="normal" font="default" size="100%">Ellinor, Patrick T</style></author><author><style face="normal" font="default" size="100%">Irvin, Marguerite R</style></author><author><style face="normal" font="default" size="100%">Fingerlin, Tasha E</style></author><author><style face="normal" font="default" size="100%">Raffield, Laura M</style></author><author><style face="normal" font="default" size="100%">Armasu, Sebastian M</style></author><author><style face="normal" font="default" size="100%">Wheeler, Marsha M</style></author><author><style face="normal" font="default" size="100%">Sabino, Ester C</style></author><author><style face="normal" font="default" size="100%">Blangero, John</style></author><author><style face="normal" font="default" size="100%">Williams, L Keoki</style></author><author><style face="normal" font="default" size="100%">Levy, Bruce D</style></author><author><style face="normal" font="default" size="100%">Sheu, Wayne Huey-Herng</style></author><author><style face="normal" font="default" size="100%">Roden, Dan M</style></author><author><style face="normal" font="default" size="100%">Boerwinkle, Eric</style></author><author><style face="normal" font="default" size="100%">Manson, JoAnn E</style></author><author><style face="normal" font="default" size="100%">Mathias, Rasika A</style></author><author><style face="normal" font="default" size="100%">Desai, Pinkal</style></author><author><style face="normal" font="default" size="100%">Taylor, Kent D</style></author><author><style face="normal" font="default" size="100%">Johnson, Andrew D</style></author><author><style face="normal" font="default" size="100%">Auer, Paul L</style></author><author><style face="normal" font="default" size="100%">Kooperberg, Charles</style></author><author><style face="normal" font="default" size="100%">Laurie, Cathy C</style></author><author><style face="normal" font="default" size="100%">Blackwell, Thomas W</style></author><author><style face="normal" font="default" size="100%">Smith, Albert V</style></author><author><style face="normal" font="default" size="100%">Zhao, Hongyu</style></author><author><style face="normal" font="default" size="100%">Lange, Ethan</style></author><author><style face="normal" font="default" size="100%">Lange, Leslie</style></author><author><style face="normal" font="default" size="100%">Rich, Stephen S</style></author><author><style face="normal" font="default" size="100%">Rotter, Jerome I</style></author><author><style face="normal" font="default" size="100%">Wilson, James G</style></author><author><style face="normal" font="default" size="100%">Scheet, Paul</style></author><author><style face="normal" font="default" size="100%">Kitzman, Jacob O</style></author><author><style face="normal" font="default" size="100%">Lander, Eric S</style></author><author><style face="normal" font="default" size="100%">Engreitz, Jesse M</style></author><author><style face="normal" font="default" size="100%">Ebert, Benjamin L</style></author><author><style face="normal" font="default" size="100%">Reiner, Alexander P</style></author><author><style face="normal" font="default" size="100%">Jaiswal, Siddhartha</style></author><author><style face="normal" font="default" size="100%">Abecasis, Gonçalo</style></author><author><style face="normal" font="default" size="100%">Sankaran, Vijay G</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author><author><style face="normal" font="default" size="100%">Natarajan, Pradeep</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">NHLBI Trans-Omics for Precision Medicine Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Inherited causes of clonal haematopoiesis in 97,691 whole genomes.</style></title><secondary-title><style face="normal" font="default" size="100%">Nature</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nature</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Africa</style></keyword><keyword><style  face="normal" font="default" size="100%">African Continental Ancestry Group</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged, 80 and over</style></keyword><keyword><style  face="normal" font="default" size="100%">alpha Karyopherins</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Self Renewal</style></keyword><keyword><style  face="normal" font="default" size="100%">Clonal Hematopoiesis</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA-Binding Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Human</style></keyword><keyword><style  face="normal" font="default" size="100%">Germ-Line Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Hematopoietic Stem Cells</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Intracellular Signaling Peptides and Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">National Heart, Lung, and Blood Institute (U.S.)</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Precision Medicine</style></keyword><keyword><style  face="normal" font="default" size="100%">Proto-Oncogene Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">Tripartite Motif Proteins</style></keyword><keyword><style  face="normal" font="default" size="100%">United States</style></keyword><keyword><style  face="normal" font="default" size="100%">Whole Genome Sequencing</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 10</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">586</style></volume><pages><style face="normal" font="default" size="100%">763-768</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer and coronary heart disease-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP). Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">7831</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/33057201?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Satterstrom, F Kyle</style></author><author><style face="normal" font="default" size="100%">Kosmicki, Jack A</style></author><author><style face="normal" font="default" size="100%">Wang, Jiebiao</style></author><author><style face="normal" font="default" size="100%">Breen, Michael S</style></author><author><style face="normal" font="default" size="100%">De Rubeis, Silvia</style></author><author><style face="normal" font="default" size="100%">An, Joon-Yong</style></author><author><style face="normal" font="default" size="100%">Peng, Minshi</style></author><author><style face="normal" font="default" size="100%">Collins, Ryan</style></author><author><style face="normal" font="default" size="100%">Grove, Jakob</style></author><author><style face="normal" font="default" size="100%">Klei, Lambertus</style></author><author><style face="normal" font="default" size="100%">Stevens, Christine</style></author><author><style face="normal" font="default" size="100%">Reichert, Jennifer</style></author><author><style face="normal" font="default" size="100%">Mulhern, Maureen S</style></author><author><style face="normal" font="default" size="100%">Artomov, Mykyta</style></author><author><style face="normal" font="default" size="100%">Gerges, Sherif</style></author><author><style face="normal" font="default" size="100%">Sheppard, Brooke</style></author><author><style face="normal" font="default" size="100%">Xu, Xinyi</style></author><author><style face="normal" font="default" size="100%">Bhaduri, Aparna</style></author><author><style face="normal" font="default" size="100%">Norman, Utku</style></author><author><style face="normal" font="default" size="100%">Brand, Harrison</style></author><author><style face="normal" font="default" size="100%">Schwartz, Grace</style></author><author><style face="normal" font="default" size="100%">Nguyen, Rachel</style></author><author><style face="normal" font="default" size="100%">Guerrero, Elizabeth E</style></author><author><style face="normal" font="default" size="100%">Dias, Caroline</style></author><author><style face="normal" font="default" size="100%">Betancur, Catalina</style></author><author><style face="normal" font="default" size="100%">Cook, Edwin H</style></author><author><style face="normal" font="default" size="100%">Gallagher, Louise</style></author><author><style face="normal" font="default" size="100%">Gill, Michael</style></author><author><style face="normal" font="default" size="100%">Sutcliffe, James S</style></author><author><style face="normal" font="default" size="100%">Thurm, Audrey</style></author><author><style face="normal" font="default" size="100%">Zwick, Michael E</style></author><author><style face="normal" font="default" size="100%">Børglum, Anders D</style></author><author><style face="normal" font="default" size="100%">State, Matthew W</style></author><author><style face="normal" font="default" size="100%">Cicek, A Ercument</style></author><author><style face="normal" font="default" size="100%">Talkowski, Michael E</style></author><author><style face="normal" font="default" size="100%">Cutler, David J</style></author><author><style face="normal" font="default" size="100%">Devlin, Bernie</style></author><author><style face="normal" font="default" size="100%">Sanders, Stephan J</style></author><author><style face="normal" font="default" size="100%">Roeder, Kathryn</style></author><author><style face="normal" font="default" size="100%">Daly, Mark J</style></author><author><style face="normal" font="default" size="100%">Buxbaum, Joseph D</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">Autism Sequencing Consortium</style></author><author><style face="normal" font="default" size="100%">iPSYCH-Broad Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism.</style></title><secondary-title><style face="normal" font="default" size="100%">Cell</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Cell</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Autistic Disorder</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Cell Lineage</style></keyword><keyword><style  face="normal" font="default" size="100%">Cerebral Cortex</style></keyword><keyword><style  face="normal" font="default" size="100%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Exome</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Expression Regulation, Developmental</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation, Missense</style></keyword><keyword><style  face="normal" font="default" size="100%">Neurobiology</style></keyword><keyword><style  face="normal" font="default" size="100%">Neurons</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Sex Factors</style></keyword><keyword><style  face="normal" font="default" size="100%">Single-Cell Analysis</style></keyword><keyword><style  face="normal" font="default" size="100%">Whole Exome Sequencing</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 02 06</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">180</style></volume><pages><style face="normal" font="default" size="100%">568-584.e23</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n = 35,584 total samples, 11,986 with ASD). Using an enhanced analytical framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate of 0.1 or less. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained to have severe neurodevelopmental delay, whereas 53 show higher frequencies in individuals ascertained to have ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In cells from the human cortex, expression of risk genes is enriched in excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory-inhibitory imbalance underlying ASD.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/31981491?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chun, Sung</style></author><author><style face="normal" font="default" size="100%">Imakaev, Maxim</style></author><author><style face="normal" font="default" size="100%">Hui, Daniel</style></author><author><style face="normal" font="default" size="100%">Patsopoulos, Nikolaos A</style></author><author><style face="normal" font="default" size="100%">Neale, Benjamin M</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author><author><style face="normal" font="default" size="100%">Stitziel, Nathan O</style></author><author><style face="normal" font="default" size="100%">Sunyaev, Shamil R</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Non-parametric Polygenic Risk Prediction via Partitioned GWAS Summary Statistics.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Cohort Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Diabetes Mellitus, Type 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Genotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Linkage Disequilibrium</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Genetic</style></keyword><keyword><style  face="normal" font="default" size="100%">Multifactorial Inheritance</style></keyword><keyword><style  face="normal" font="default" size="100%">Phenotype</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword><keyword><style  face="normal" font="default" size="100%">Quantitative Trait Loci</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 07 02</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">107</style></volume><pages><style face="normal" font="default" size="100%">46-59</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;In complex trait genetics, the ability to predict phenotype from genotype is the ultimate measure of our understanding of genetic architecture underlying the heritability of a trait. A complete understanding of the genetic basis of a trait should allow for predictive methods with accuracies approaching the trait's heritability. The highly polygenic nature of quantitative traits and most common phenotypes has motivated the development of statistical strategies focused on combining myriad individually non-significant genetic effects. Now that predictive accuracies are improving, there is a growing interest in the practical utility of such methods for predicting risk of common diseases responsive to early therapeutic intervention. However, existing methods require individual-level genotypes or depend on accurately specifying the genetic architecture underlying each disease to be predicted. Here, we propose a polygenic risk prediction method that does not require explicitly modeling any underlying genetic architecture. We start with summary statistics in the form of SNP effect sizes from a large GWAS cohort. We then remove the correlation structure across summary statistics arising due to linkage disequilibrium and apply a piecewise linear interpolation on conditional mean effects. In both simulated and real datasets, this new non-parametric shrinkage (NPS) method can reliably allow for linkage disequilibrium in summary statistics of 5 million dense genome-wide markers and consistently improves prediction accuracy. We show that NPS improves the identification of groups at high risk for breast cancer, type 2 diabetes, inflammatory bowel disease, and coronary heart disease, all of which have available early intervention or prevention treatments.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32470373?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Grenn, Francis P</style></author><author><style face="normal" font="default" size="100%">Kim, Jonggeol J</style></author><author><style face="normal" font="default" size="100%">Makarious, Mary B</style></author><author><style face="normal" font="default" size="100%">Iwaki, Hirotaka</style></author><author><style face="normal" font="default" size="100%">Illarionova, Anastasia</style></author><author><style face="normal" font="default" size="100%">Brolin, Kajsa</style></author><author><style face="normal" font="default" size="100%">Kluss, Jillian H</style></author><author><style face="normal" font="default" size="100%">Schumacher-Schuh, Artur F</style></author><author><style face="normal" font="default" size="100%">Leonard, Hampton</style></author><author><style face="normal" font="default" size="100%">Faghri, Faraz</style></author><author><style face="normal" font="default" size="100%">Billingsley, Kimberley</style></author><author><style face="normal" font="default" size="100%">Krohn, Lynne</style></author><author><style face="normal" font="default" size="100%">Hall, Ashley</style></author><author><style face="normal" font="default" size="100%">Diez-Fairen, Monica</style></author><author><style face="normal" font="default" size="100%">Periñán, Maria Teresa</style></author><author><style face="normal" font="default" size="100%">Foo, Jia Nee</style></author><author><style face="normal" font="default" size="100%">Sandor, Cynthia</style></author><author><style face="normal" font="default" size="100%">Webber, Caleb</style></author><author><style face="normal" font="default" size="100%">Fiske, Brian K</style></author><author><style face="normal" font="default" size="100%">Gibbs, J Raphael</style></author><author><style face="normal" font="default" size="100%">Nalls, Mike A</style></author><author><style face="normal" font="default" size="100%">Singleton, Andrew B</style></author><author><style face="normal" font="default" size="100%">Bandres-Ciga, Sara</style></author><author><style face="normal" font="default" size="100%">Reed, Xylena</style></author><author><style face="normal" font="default" size="100%">Blauwendraat, Cornelis</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">International Parkinson's Disease Genomics Consortium (IPDGC)</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">The Parkinson's Disease Genome-Wide Association Study Locus Browser.</style></title><secondary-title><style face="normal" font="default" size="100%">Mov Disord</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Mov Disord</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Age of Onset</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Neurodegenerative Diseases</style></keyword><keyword><style  face="normal" font="default" size="100%">Parkinson Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Risk Factors</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 11</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">35</style></volume><pages><style face="normal" font="default" size="100%">2056-2067</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets.&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">11</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32864809?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Ferraro, Nicole M</style></author><author><style face="normal" font="default" size="100%">Strober, Benjamin J</style></author><author><style face="normal" font="default" size="100%">Einson, Jonah</style></author><author><style face="normal" font="default" size="100%">Abell, Nathan S</style></author><author><style face="normal" font="default" size="100%">Aguet, François</style></author><author><style face="normal" font="default" size="100%">Barbeira, Alvaro N</style></author><author><style face="normal" font="default" size="100%">Brandt, Margot</style></author><author><style face="normal" font="default" size="100%">Bucan, Maja</style></author><author><style face="normal" font="default" size="100%">Castel, Stephane E</style></author><author><style face="normal" font="default" size="100%">Davis, Joe R</style></author><author><style face="normal" font="default" size="100%">Greenwald, Emily</style></author><author><style face="normal" font="default" size="100%">Hess, Gaelen T</style></author><author><style face="normal" font="default" size="100%">Hilliard, Austin T</style></author><author><style face="normal" font="default" size="100%">Kember, Rachel L</style></author><author><style face="normal" font="default" size="100%">Kotis, Bence</style></author><author><style face="normal" font="default" size="100%">Park, YoSon</style></author><author><style face="normal" font="default" size="100%">Peloso, Gina</style></author><author><style face="normal" font="default" size="100%">Ramdas, Shweta</style></author><author><style face="normal" font="default" size="100%">Scott, Alexandra J</style></author><author><style face="normal" font="default" size="100%">Smail, Craig</style></author><author><style face="normal" font="default" size="100%">Tsang, Emily K</style></author><author><style face="normal" font="default" size="100%">Zekavat, Seyedeh M</style></author><author><style face="normal" font="default" size="100%">Ziosi, Marcello</style></author><author><style face="normal" font="default" size="100%">Ardlie, Kristin G</style></author><author><style face="normal" font="default" size="100%">Assimes, Themistocles L</style></author><author><style face="normal" font="default" size="100%">Bassik, Michael C</style></author><author><style face="normal" font="default" size="100%">Brown, Christopher D</style></author><author><style face="normal" font="default" size="100%">Correa, Adolfo</style></author><author><style face="normal" font="default" size="100%">Hall, Ira</style></author><author><style face="normal" font="default" size="100%">Im, Hae Kyung</style></author><author><style face="normal" font="default" size="100%">Li, Xin</style></author><author><style face="normal" font="default" size="100%">Natarajan, Pradeep</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author><author><style face="normal" font="default" size="100%">Mohammadi, Pejman</style></author><author><style face="normal" font="default" size="100%">Montgomery, Stephen B</style></author><author><style face="normal" font="default" size="100%">Battle, Alexis</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">TOPMed Lipids Working Group</style></author><author><style face="normal" font="default" size="100%">GTEx Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">Transcriptomic signatures across human tissues identify functional rare genetic variation.</style></title><secondary-title><style face="normal" font="default" size="100%">Science</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Science</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Genetic Variation</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Human</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Multifactorial Inheritance</style></keyword><keyword><style  face="normal" font="default" size="100%">Organ Specificity</style></keyword><keyword><style  face="normal" font="default" size="100%">Transcriptome</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 09 11</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">369</style></volume><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Rare genetic variants are abundant across the human genome, and identifying their function and phenotypic impact is a major challenge. Measuring aberrant gene expression has aided in identifying functional, large-effect rare variants (RVs). Here, we expanded detection of genetically driven transcriptome abnormalities by analyzing gene expression, allele-specific expression, and alternative splicing from multitissue RNA-sequencing data, and demonstrate that each signal informs unique classes of RVs. We developed Watershed, a probabilistic model that integrates multiple genomic and transcriptomic signals to predict variant function, validated these predictions in additional cohorts and through experimental assays, and used them to assess RVs in the UK Biobank, the Million Veterans Program, and the Jackson Heart Study. Our results link thousands of RVs to diverse molecular effects and provide evidence to associate RVs affecting the transcriptome with human traits.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6509</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32913073?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Wang, Minxian</style></author><author><style face="normal" font="default" size="100%">Menon, Ramesh</style></author><author><style face="normal" font="default" size="100%">Mishra, Sanghamitra</style></author><author><style face="normal" font="default" size="100%">Patel, Aniruddh P</style></author><author><style face="normal" font="default" size="100%">Chaffin, Mark</style></author><author><style face="normal" font="default" size="100%">Tanneeru, Deepak</style></author><author><style face="normal" font="default" size="100%">Deshmukh, Manjari</style></author><author><style face="normal" font="default" size="100%">Mathew, Oshin</style></author><author><style face="normal" font="default" size="100%">Apte, Sanika</style></author><author><style face="normal" font="default" size="100%">Devanboo, Christina S</style></author><author><style face="normal" font="default" size="100%">Sundaram, Sumathi</style></author><author><style face="normal" font="default" size="100%">Lakshmipathy, Praveena</style></author><author><style face="normal" font="default" size="100%">Murugan, Sakthivel</style></author><author><style face="normal" font="default" size="100%">Sharma, Krishna Kumar</style></author><author><style face="normal" font="default" size="100%">Rajendran, Karthikeyan</style></author><author><style face="normal" font="default" size="100%">Santhosh, Sam</style></author><author><style face="normal" font="default" size="100%">Thachathodiyl, Rajesh</style></author><author><style face="normal" font="default" size="100%">Ahamed, Hisham</style></author><author><style face="normal" font="default" size="100%">Balegadde, Aniketh Vijay</style></author><author><style face="normal" font="default" size="100%">Alexander, Thomas</style></author><author><style face="normal" font="default" size="100%">Swaminathan, Krishnan</style></author><author><style face="normal" font="default" size="100%">Gupta, Rajeev</style></author><author><style face="normal" font="default" size="100%">Mullasari, Ajit S</style></author><author><style face="normal" font="default" size="100%">Sigamani, Alben</style></author><author><style face="normal" font="default" size="100%">Kanchi, Muralidhar</style></author><author><style face="normal" font="default" size="100%">Peterson, Andrew S</style></author><author><style face="normal" font="default" size="100%">Butterworth, Adam S</style></author><author><style face="normal" font="default" size="100%">Danesh, John</style></author><author><style face="normal" font="default" size="100%">Di Angelantonio, Emanuele</style></author><author><style face="normal" font="default" size="100%">Naheed, Aliya</style></author><author><style face="normal" font="default" size="100%">Inouye, Michael</style></author><author><style face="normal" font="default" size="100%">Chowdhury, Rajiv</style></author><author><style face="normal" font="default" size="100%">Vedam, Ramprasad L</style></author><author><style face="normal" font="default" size="100%">Kathiresan, Sekar</style></author><author><style face="normal" font="default" size="100%">Gupta, Ravi</style></author><author><style face="normal" font="default" size="100%">Khera, Amit V</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Validation of a Genome-Wide Polygenic Score for Coronary Artery Disease in South Asians.</style></title><secondary-title><style face="normal" font="default" size="100%">J Am Coll Cardiol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">J Am Coll Cardiol</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adult</style></keyword><keyword><style  face="normal" font="default" size="100%">Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Bangladesh</style></keyword><keyword><style  face="normal" font="default" size="100%">Case-Control Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Coronary Artery Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome-Wide Association Study</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">India</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Middle Aged</style></keyword><keyword><style  face="normal" font="default" size="100%">Multifactorial Inheritance</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2020 08 11</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">76</style></volume><pages><style face="normal" font="default" size="100%">703-714</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;BACKGROUND: &lt;/b&gt;Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population.&lt;/p&gt;&lt;p&gt;&lt;b&gt;OBJECTIVES: &lt;/b&gt;This analysis used summary statistics from a prior genome-wide association study to derive a new GPS for South Asians.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;This GPS was validated in 7,244 South Asian UK Biobank participants and tested in 491 individuals from a case-control study in Bangladesh. Next, a static ancestry and GPS reference distribution was built using whole-genome sequencing from 1,522 Indian individuals, and a framework was tested for projecting individuals onto this static ancestry and GPS reference distribution using 1,800 CAD cases and 1,163 control subjects newly recruited in India.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;The GPS, containing 6,630,150 common DNA variants, had an odds ratio (OR) per SD of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p &lt; 0.001 for each). Next, individuals of the Indian case-control study were projected onto static reference distributions, observing an OR/SD of 1.66 (p &lt; 0.001). Compared with the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPS distribution-ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p &lt; 0.05 for each).&lt;/p&gt;&lt;p&gt;&lt;b&gt;CONCLUSIONS: &lt;/b&gt;The new GPS has been developed and tested using 3 distinct South Asian studies, and provides a generalizable framework for ancestry-specific GPS assessment.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/32762905?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Punetha, Jaya</style></author><author><style face="normal" font="default" size="100%">Karaca, Ender</style></author><author><style face="normal" font="default" size="100%">Gezdirici, Alper</style></author><author><style face="normal" font="default" size="100%">Lamont, Ryan E</style></author><author><style face="normal" font="default" size="100%">Pehlivan, Davut</style></author><author><style face="normal" font="default" size="100%">Marafi, Dana</style></author><author><style face="normal" font="default" size="100%">Appendino, Juan P</style></author><author><style face="normal" font="default" size="100%">Hunter, Jill V</style></author><author><style face="normal" font="default" size="100%">Akdemir, Zeynep C</style></author><author><style face="normal" font="default" size="100%">Fatih, Jawid M</style></author><author><style face="normal" font="default" size="100%">Jhangiani, Shalini N</style></author><author><style face="normal" font="default" size="100%">Gibbs, Richard A</style></author><author><style face="normal" font="default" size="100%">Innes, A Micheil</style></author><author><style face="normal" font="default" size="100%">Posey, Jennifer E</style></author><author><style face="normal" font="default" size="100%">Lupski, James R</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Biallelic CACNA2D2 variants in epileptic encephalopathy and cerebellar atrophy.</style></title><secondary-title><style face="normal" font="default" size="100%">Ann Clin Transl Neurol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Ann Clin Transl Neurol</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Aug</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">6</style></volume><pages><style face="normal" font="default" size="100%">1395-1406</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;&lt;b&gt;OBJECTIVE: &lt;/b&gt;To characterize the molecular and clinical phenotypic basis of developmental and epileptic encephalopathies caused by rare biallelic variants in CACNA2D2.&lt;/p&gt;&lt;p&gt;&lt;b&gt;METHODS: &lt;/b&gt;Two affected individuals from a family with clinical features of early onset epileptic encephalopathy were recruited for exome sequencing at the Centers for Mendelian Genomics to identify their molecular diagnosis. GeneMatcher facilitated identification of a second family with a shared candidate disease gene identified through clinical gene panel-based testing.&lt;/p&gt;&lt;p&gt;&lt;b&gt;RESULTS: &lt;/b&gt;Rare biallelic CACNA2D2 variants have been previously reported in three families with developmental and epileptic encephalopathy, and one family with congenital ataxia. We identified three individuals in two unrelated families with novel homozygous rare variants in CACNA2D2 with clinical features of developmental and epileptic encephalopathy and cerebellar atrophy. Family 1 includes two affected siblings with a likely damaging homozygous rare missense variant c.1778G&gt;C; p.(Arg593Pro) in CACNA2D2. Family 2 includes a proband with a homozygous rare nonsense variant c.485_486del; p.(Tyr162Ter) in CACNA2D2. We compared clinical and molecular findings from all nine individuals reported to date and note that cerebellar atrophy is shared among all.&lt;/p&gt;&lt;p&gt;&lt;b&gt;INTERPRETATION: &lt;/b&gt;Our study supports the candidacy of CACNA2D2 as a disease gene associated with a phenotypic spectrum of neurological disease that include features of developmental and epileptic encephalopathy, ataxia, and cerebellar atrophy. Age at presentation may affect apparent penetrance of neurogenetic trait manifestations and of a particular clinical neurological endophenotype, for example, seizures or ataxia.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">8</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/31402629?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">van Karnebeek, Clara D M</style></author><author><style face="normal" font="default" size="100%">Ramos, Rúben J</style></author><author><style face="normal" font="default" size="100%">Wen, Xiao-Yan</style></author><author><style face="normal" font="default" size="100%">Tarailo-Graovac, Maja</style></author><author><style face="normal" font="default" size="100%">Gleeson, Joseph G</style></author><author><style face="normal" font="default" size="100%">Skrypnyk, Cristina</style></author><author><style face="normal" font="default" size="100%">Brand-Arzamendi, Koroboshka</style></author><author><style face="normal" font="default" size="100%">Karbassi, Farhad</style></author><author><style face="normal" font="default" size="100%">Issa, Mahmoud Y</style></author><author><style face="normal" font="default" size="100%">van der Lee, Robin</style></author><author><style face="normal" font="default" size="100%">Drögemöller, Britt I</style></author><author><style face="normal" font="default" size="100%">Koster, Janet</style></author><author><style face="normal" font="default" size="100%">Rousseau, Justine</style></author><author><style face="normal" font="default" size="100%">Campeau, Philippe M</style></author><author><style face="normal" font="default" size="100%">Wang, Youdong</style></author><author><style face="normal" font="default" size="100%">Cao, Feng</style></author><author><style face="normal" font="default" size="100%">Li, Meng</style></author><author><style face="normal" font="default" size="100%">Ruiter, Jos</style></author><author><style face="normal" font="default" size="100%">Ciapaite, Jolita</style></author><author><style face="normal" font="default" size="100%">Kluijtmans, Leo A J</style></author><author><style face="normal" font="default" size="100%">Willemsen, Michel A A P</style></author><author><style face="normal" font="default" size="100%">Jans, Judith J</style></author><author><style face="normal" font="default" size="100%">Ross, Colin J</style></author><author><style face="normal" font="default" size="100%">Wintjes, Liesbeth T</style></author><author><style face="normal" font="default" size="100%">Rodenburg, Richard J</style></author><author><style face="normal" font="default" size="100%">Huigen, Marleen C D G</style></author><author><style face="normal" font="default" size="100%">Jia, Zhengping</style></author><author><style face="normal" font="default" size="100%">Waterham, Hans R</style></author><author><style face="normal" font="default" size="100%">Wasserman, Wyeth W</style></author><author><style face="normal" font="default" size="100%">Wanders, Ronald J A</style></author><author><style face="normal" font="default" size="100%">Verhoeven-Duif, Nanda M</style></author><author><style face="normal" font="default" size="100%">Zaki, Maha S</style></author><author><style face="normal" font="default" size="100%">Wevers, Ron A</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Hum. Genet.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Sep 05</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">105</style></volume><pages><style face="normal" font="default" size="100%">534-548</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Early-infantile encephalopathies with epilepsy are devastating conditions mandating an accurate diagnosis to guide proper management. Whole-exome sequencing was used to investigate the disease etiology in four children from independent families with intellectual disability and epilepsy, revealing bi-allelic GOT2 mutations. In-depth metabolic studies in individual 1 showed low plasma serine, hypercitrullinemia, hyperlactatemia, and hyperammonemia. The epilepsy was serine and pyridoxine responsive. Functional consequences of observed mutations were tested by measuring enzyme activity and by cell and animal models. Zebrafish and mouse models were used to validate brain developmental and functional defects and to test therapeutic strategies. GOT2 encodes the mitochondrial glutamate oxaloacetate transaminase. GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. GOT2, a member of the malate-aspartate shuttle, plays an essential role in the intracellular NAD(H) redox balance. De novo serine biosynthesis was impaired in fibroblasts with GOT2 mutations and GOT2-knockout HEK293 cells. Correcting the highly oxidized cytosolic NAD-redox state by pyruvate supplementation restored serine biosynthesis in GOT2-deficient cells. Knockdown of got2a in zebrafish resulted in a brain developmental defect associated with seizure-like electroencephalography spikes, which could be rescued by supplying pyridoxine in embryo water. Both pyridoxine and serine synergistically rescued embryonic developmental defects in zebrafish got2a morphants. The two treated individuals reacted favorably to their treatment. Our data provide a mechanistic basis for the biochemical abnormalities in GOT2 deficiency that may also hold for other MAS defects.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/31422819?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Mohammadi, Pejman</style></author><author><style face="normal" font="default" size="100%">Castel, Stephane E</style></author><author><style face="normal" font="default" size="100%">Cummings, Beryl B</style></author><author><style face="normal" font="default" size="100%">Einson, Jonah</style></author><author><style face="normal" font="default" size="100%">Sousa, Christina</style></author><author><style face="normal" font="default" size="100%">Hoffman, Paul</style></author><author><style face="normal" font="default" size="100%">Donkervoort, Sandra</style></author><author><style face="normal" font="default" size="100%">Jiang, Zhuoxun</style></author><author><style face="normal" font="default" size="100%">Mohassel, Payam</style></author><author><style face="normal" font="default" size="100%">Foley, A Reghan</style></author><author><style face="normal" font="default" size="100%">Wheeler, Heather E</style></author><author><style face="normal" font="default" size="100%">Im, Hae Kyung</style></author><author><style face="normal" font="default" size="100%">Bonnemann, Carsten G</style></author><author><style face="normal" font="default" size="100%">MacArthur, Daniel G</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genetic regulatory variation in populations informs transcriptome analysis in rare disease.</style></title><secondary-title><style face="normal" font="default" size="100%">Science</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Science</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 10 18</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">366</style></volume><pages><style face="normal" font="default" size="100%">351-356</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Transcriptome data can facilitate the interpretation of the effects of rare genetic variants. Here, we introduce ANEVA (analysis of expression variation) to quantify genetic variation in gene dosage from allelic expression (AE) data in a population. Application of ANEVA to the Genotype-Tissues Expression (GTEx) data showed that this variance estimate is robust and correlated with selective constraint in a gene. Using these variance estimates in a dosage outlier test (ANEVA-DOT) applied to AE data from 70 Mendelian muscular disease patients showed accuracy in detecting genes with pathogenic variants in previously resolved cases and led to one confirmed and several potential new diagnoses. Using our reference estimates from GTEx data, ANEVA-DOT can be incorporated in rare disease diagnostic pipelines to use RNA-sequencing data more effectively.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">6463</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/31601707?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Connaughton, Dervla M</style></author><author><style face="normal" font="default" size="100%">Kennedy, Claire</style></author><author><style face="normal" font="default" size="100%">Shril, Shirlee</style></author><author><style face="normal" font="default" size="100%">Mann, Nina</style></author><author><style face="normal" font="default" size="100%">Murray, Susan L</style></author><author><style face="normal" font="default" size="100%">Williams, Patrick A</style></author><author><style face="normal" font="default" size="100%">Conlon, Eoin</style></author><author><style face="normal" font="default" size="100%">Nakayama, Makiko</style></author><author><style face="normal" font="default" size="100%">van der Ven, Amelie T</style></author><author><style face="normal" font="default" size="100%">Ityel, Hadas</style></author><author><style face="normal" font="default" size="100%">Kause, Franziska</style></author><author><style face="normal" font="default" size="100%">Kolvenbach, Caroline M</style></author><author><style face="normal" font="default" size="100%">Dai, Rufeng</style></author><author><style face="normal" font="default" size="100%">Vivante, Asaf</style></author><author><style face="normal" font="default" size="100%">Braun, Daniela A</style></author><author><style face="normal" font="default" size="100%">Schneider, Ronen</style></author><author><style face="normal" font="default" size="100%">Kitzler, Thomas M</style></author><author><style face="normal" font="default" size="100%">Moloney, Brona</style></author><author><style face="normal" font="default" size="100%">Moran, Conor P</style></author><author><style face="normal" font="default" size="100%">Smyth, John S</style></author><author><style face="normal" font="default" size="100%">Kennedy, Alan</style></author><author><style face="normal" font="default" size="100%">Benson, Katherine</style></author><author><style face="normal" font="default" size="100%">Stapleton, Caragh</style></author><author><style face="normal" font="default" size="100%">Denton, Mark</style></author><author><style face="normal" font="default" size="100%">Magee, Colm</style></author><author><style face="normal" font="default" size="100%">O'Seaghdha, Conall M</style></author><author><style face="normal" font="default" size="100%">Plant, William D</style></author><author><style face="normal" font="default" size="100%">Griffin, Matthew D</style></author><author><style face="normal" font="default" size="100%">Awan, Atif</style></author><author><style face="normal" font="default" size="100%">Sweeney, Clodagh</style></author><author><style face="normal" font="default" size="100%">Mane, Shrikant M</style></author><author><style face="normal" font="default" size="100%">Lifton, Richard P</style></author><author><style face="normal" font="default" size="100%">Griffin, Brenda</style></author><author><style face="normal" font="default" size="100%">Leavey, Sean</style></author><author><style face="normal" font="default" size="100%">Casserly, Liam</style></author><author><style face="normal" font="default" size="100%">de Freitas, Declan G</style></author><author><style face="normal" font="default" size="100%">Holian, John</style></author><author><style face="normal" font="default" size="100%">Dorman, Anthony</style></author><author><style face="normal" font="default" size="100%">Doyle, Brendan</style></author><author><style face="normal" font="default" size="100%">Lavin, Peter J</style></author><author><style face="normal" font="default" size="100%">Little, Mark A</style></author><author><style face="normal" font="default" size="100%">Conlon, Peter J</style></author><author><style face="normal" font="default" size="100%">Hildebrandt, Friedhelm</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Monogenic causes of chronic kidney disease in adults.</style></title><secondary-title><style face="normal" font="default" size="100%">Kidney Int</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Kidney Int.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Apr</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">95</style></volume><pages><style face="normal" font="default" size="100%">914-928</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">4</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/30773290?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Donkervoort, S</style></author><author><style face="normal" font="default" size="100%">Sabouny, R</style></author><author><style face="normal" font="default" size="100%">Yun, P</style></author><author><style face="normal" font="default" size="100%">Gauquelin, L</style></author><author><style face="normal" font="default" size="100%">Chao, K R</style></author><author><style face="normal" font="default" size="100%">Hu, Y</style></author><author><style face="normal" font="default" size="100%">Al Khatib, I</style></author><author><style face="normal" font="default" size="100%">Töpf, A</style></author><author><style face="normal" font="default" size="100%">Mohassel, P</style></author><author><style face="normal" font="default" size="100%">Cummings, B B</style></author><author><style face="normal" font="default" size="100%">Kaur, R</style></author><author><style face="normal" font="default" size="100%">Saade, D</style></author><author><style face="normal" font="default" size="100%">Moore, S A</style></author><author><style face="normal" font="default" size="100%">Waddell, L B</style></author><author><style face="normal" font="default" size="100%">Farrar, M A</style></author><author><style face="normal" font="default" size="100%">Goodrich, J K</style></author><author><style face="normal" font="default" size="100%">Uapinyoying, P</style></author><author><style face="normal" font="default" size="100%">Chan, S H S</style></author><author><style face="normal" font="default" size="100%">Javed, A</style></author><author><style face="normal" font="default" size="100%">Leach, M E</style></author><author><style face="normal" font="default" size="100%">Karachunski, P</style></author><author><style face="normal" font="default" size="100%">Dalton, J</style></author><author><style face="normal" font="default" size="100%">Medne, L</style></author><author><style face="normal" font="default" size="100%">Harper, A</style></author><author><style face="normal" font="default" size="100%">Thompson, C</style></author><author><style face="normal" font="default" size="100%">Thiffault, I</style></author><author><style face="normal" font="default" size="100%">Specht, S</style></author><author><style face="normal" font="default" size="100%">Lamont, R E</style></author><author><style face="normal" font="default" size="100%">Saunders, C</style></author><author><style face="normal" font="default" size="100%">Racher, H</style></author><author><style face="normal" font="default" size="100%">Bernier, F P</style></author><author><style face="normal" font="default" size="100%">Mowat, D</style></author><author><style face="normal" font="default" size="100%">Witting, N</style></author><author><style face="normal" font="default" size="100%">Vissing, J</style></author><author><style face="normal" font="default" size="100%">Hanson, R</style></author><author><style face="normal" font="default" size="100%">Coffman, K A</style></author><author><style face="normal" font="default" size="100%">Hainlen, M</style></author><author><style face="normal" font="default" size="100%">Parboosingh, J S</style></author><author><style face="normal" font="default" size="100%">Carnevale, A</style></author><author><style face="normal" font="default" size="100%">Yoon, G</style></author><author><style face="normal" font="default" size="100%">Schnur, R E</style></author><author><style face="normal" font="default" size="100%">Boycott, K M</style></author><author><style face="normal" font="default" size="100%">Mah, J K</style></author><author><style face="normal" font="default" size="100%">Straub, V</style></author><author><style face="normal" font="default" size="100%">Foley, A Reghan</style></author><author><style face="normal" font="default" size="100%">Innes, A M</style></author><author><style face="normal" font="default" size="100%">Bönnemann, C G</style></author><author><style face="normal" font="default" size="100%">Shutt, T E</style></author></authors><translated-authors><author><style face="normal" font="default" size="100%">Care4Rare Canada Consortium</style></author></translated-authors></contributors><titles><title><style face="normal" font="default" size="100%">MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement.</style></title><secondary-title><style face="normal" font="default" size="100%">Acta Neuropathol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Acta Neuropathol.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Aug 29</style></date></pub-dates></dates><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;MSTO1 encodes a cytosolic mitochondrial fusion protein, misato homolog 1 or MSTO1. While the full genotype-phenotype spectrum remains to be explored, pathogenic variants in MSTO1 have recently been reported in a small number of patients presenting with a phenotype of cerebellar ataxia, congenital muscle involvement with histologic findings ranging from myopathic to dystrophic and pigmentary retinopathy. The proposed underlying pathogenic mechanism of MSTO1-related disease is suggestive of impaired mitochondrial fusion secondary to a loss of function of MSTO1. Disorders of mitochondrial fusion and fission have been shown to also lead to mitochondrial DNA (mtDNA) depletion, linking them to the mtDNA depletion syndromes, a clinically and genetically diverse class of mitochondrial diseases characterized by a reduction of cellular mtDNA content. However, the consequences of pathogenic variants in MSTO1 on mtDNA maintenance remain poorly understood. We present extensive phenotypic and genetic data from 12 independent families, including 15 new patients harbouring a broad array of bi-allelic MSTO1 pathogenic variants, and we provide functional characterization from seven MSTO1-related disease patient fibroblasts. Bi-allelic loss-of-function variants in MSTO1 manifest clinically with a remarkably consistent phenotype of childhood-onset muscular dystrophy, corticospinal tract dysfunction and early-onset non-progressive cerebellar atrophy. MSTO1 protein was not detectable in the cultured fibroblasts of all seven patients evaluated, suggesting that pathogenic variants result in a loss of protein expression and/or affect protein stability. Consistent with impaired mitochondrial fusion, mitochondrial networks in fibroblasts were found to be fragmented. Furthermore, all fibroblasts were found to have depletion of mtDNA ranging from 30 to 70% along with alterations to mtDNA nucleoids. Our data corroborate the role of MSTO1 as a mitochondrial fusion protein and highlight a previously unrecognized link to mtDNA regulation. As impaired mitochondrial fusion is a recognized cause of mtDNA depletion syndromes, this novel link to mtDNA depletion in patient fibroblasts suggests that MSTO1-deficiency should also be considered a mtDNA depletion syndrome. Thus, we provide mechanistic insight into the disease pathogenesis associated with MSTO1 mutations and further define the clinical spectrum and the natural history of MSTO1-related disease.&lt;/p&gt;</style></abstract><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/31463572?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Aldinger, Kimberly A</style></author><author><style face="normal" font="default" size="100%">Timms, Andrew E</style></author><author><style face="normal" font="default" size="100%">Thomson, Zachary</style></author><author><style face="normal" font="default" size="100%">Mirzaa, Ghayda M</style></author><author><style face="normal" font="default" size="100%">Bennett, James T</style></author><author><style face="normal" font="default" size="100%">Rosenberg, Alexander B</style></author><author><style face="normal" font="default" size="100%">Roco, Charles M</style></author><author><style face="normal" font="default" size="100%">Hirano, Matthew</style></author><author><style face="normal" font="default" size="100%">Abidi, Fatima</style></author><author><style face="normal" font="default" size="100%">Haldipur, Parthiv</style></author><author><style face="normal" font="default" size="100%">Cheng, Chi V</style></author><author><style face="normal" font="default" size="100%">Collins, Sarah</style></author><author><style face="normal" font="default" size="100%">Park, Kaylee</style></author><author><style face="normal" font="default" size="100%">Zeiger, Jordan</style></author><author><style face="normal" font="default" size="100%">Overmann, Lynne M</style></author><author><style face="normal" font="default" size="100%">Alkuraya, Fowzan S</style></author><author><style face="normal" font="default" size="100%">Biesecker, Leslie G</style></author><author><style face="normal" font="default" size="100%">Braddock, Stephen R</style></author><author><style face="normal" font="default" size="100%">Cathey, Sara</style></author><author><style face="normal" font="default" size="100%">Cho, Megan T</style></author><author><style face="normal" font="default" size="100%">Chung, Brian H Y</style></author><author><style face="normal" font="default" size="100%">Everman, David B</style></author><author><style face="normal" font="default" size="100%">Zarate, Yuri A</style></author><author><style face="normal" font="default" size="100%">Jones, Julie R</style></author><author><style face="normal" font="default" size="100%">Schwartz, Charles E</style></author><author><style face="normal" font="default" size="100%">Goldstein, Amy</style></author><author><style face="normal" font="default" size="100%">Hopkin, Robert J</style></author><author><style face="normal" font="default" size="100%">Krantz, Ian D</style></author><author><style face="normal" font="default" size="100%">Ladda, Roger L</style></author><author><style face="normal" font="default" size="100%">Leppig, Kathleen A</style></author><author><style face="normal" font="default" size="100%">McGillivray, Barbara C</style></author><author><style face="normal" font="default" size="100%">Sell, Susan</style></author><author><style face="normal" font="default" size="100%">Wusik, Katherine</style></author><author><style face="normal" font="default" size="100%">Gleeson, Joseph G</style></author><author><style face="normal" font="default" size="100%">Nickerson, Deborah A</style></author><author><style face="normal" font="default" size="100%">Bamshad, Michael J</style></author><author><style face="normal" font="default" size="100%">Gerrelli, Dianne</style></author><author><style face="normal" font="default" size="100%">Lisgo, Steven N</style></author><author><style face="normal" font="default" size="100%">Seelig, Georg</style></author><author><style face="normal" font="default" size="100%">Ishak, Gisele E</style></author><author><style face="normal" font="default" size="100%">Barkovich, A James</style></author><author><style face="normal" font="default" size="100%">Curry, Cynthia J</style></author><author><style face="normal" font="default" size="100%">Glass, Ian A</style></author><author><style face="normal" font="default" size="100%">Millen, Kathleen J</style></author><author><style face="normal" font="default" size="100%">Doherty, Dan</style></author><author><style face="normal" font="default" size="100%">Dobyns, William B</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Redefining the Etiologic Landscape of Cerebellar Malformations.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am. J. Hum. Genet.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Sep 05</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">105</style></volume><pages><style face="normal" font="default" size="100%">606-615</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Cerebellar malformations are diverse congenital anomalies frequently associated with developmental disability. Although genetic and prenatal non-genetic causes have been described, no systematic analysis has been performed. Here, we present a large-exome sequencing study of Dandy-Walker malformation (DWM) and cerebellar hypoplasia (CBLH). We performed exome sequencing in 282 individuals from 100 families with DWM or CBLH, and we established a molecular diagnosis in 36 of 100 families, with a significantly higher yield for CBLH (51%) than for DWM (16%). The 41 variants impact 27 neurodevelopmental-disorder-associated genes, thus demonstrating that CBLH and DWM are often features of monogenic neurodevelopmental disorders. Though only seven monogenic causes (19%) were identified in more than one individual, neuroimaging review of 131 additional individuals confirmed cerebellar abnormalities in 23 of 27 genetic disorders (85%). Prenatal risk factors were frequently found among individuals without a genetic diagnosis (30 of 64 individuals [47%]). Single-cell RNA sequencing of prenatal human cerebellar tissue revealed gene enrichment in neuronal and vascular cell types; this suggests that defective vasculogenesis may disrupt cerebellar development. Further, de novo gain-of-function variants in PDGFRB, a tyrosine kinase receptor essential for vascular progenitor signaling, were associated with CBLH, and this discovery links genetic and non-genetic etiologies. Our results suggest that genetic defects impact specific cerebellar cell types and implicate abnormal vascular development as a mechanism for cerebellar malformations. We also confirmed a major contribution for non-genetic prenatal factors in individuals with cerebellar abnormalities, substantially influencing diagnostic evaluation and counseling regarding recurrence risk and prognosis.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/31474318?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Castel, Stephane E</style></author><author><style face="normal" font="default" size="100%">Cervera, Alejandra</style></author><author><style face="normal" font="default" size="100%">Mohammadi, Pejman</style></author><author><style face="normal" font="default" size="100%">Aguet, François</style></author><author><style face="normal" font="default" size="100%">Reverter, Ferran</style></author><author><style face="normal" font="default" size="100%">Wolman, Aaron</style></author><author><style face="normal" font="default" size="100%">Guigo, Roderic</style></author><author><style face="normal" font="default" size="100%">Iossifov, Ivan</style></author><author><style face="normal" font="default" size="100%">Vasileva, Ana</style></author><author><style face="normal" font="default" size="100%">Lappalainen, Tuuli</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk.</style></title><secondary-title><style face="normal" font="default" size="100%">Nat Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Nat. Genet.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2018</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2018 Sep</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">50</style></volume><pages><style face="normal" font="default" size="100%">1327-1334</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Coding variants represent many of the strongest associations between genotype and phenotype; however, they exhibit inter-individual differences in effect, termed 'variable penetrance'. Here, we study how cis-regulatory variation modifies the penetrance of coding variants. Using functional genomic and genetic data from the Genotype-Tissue Expression Project (GTEx), we observed that in the general population, purifying selection has depleted haplotype combinations predicted to increase pathogenic coding variant penetrance. Conversely, in cancer and autism patients, we observed an enrichment of penetrance increasing haplotype configurations for pathogenic variants in disease-implicated genes, providing evidence that regulatory haplotype configuration of coding variants affects disease risk. Finally, we experimentally validated this model by editing a Mendelian single-nucleotide polymorphism (SNP) using CRISPR/Cas9 on distinct expression haplotypes with the transcriptome as a phenotypic readout. Our results demonstrate that joint regulatory and coding variant effects are an important part of the genetic architecture of human traits and contribute to modified penetrance of disease-causing variants.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/30127527?dopt=Abstract</style></custom1></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Turner, Tychele N</style></author><author><style face="normal" font="default" size="100%">Hormozdiari, Fereydoun</style></author><author><style face="normal" font="default" size="100%">Duyzend, Michael H</style></author><author><style face="normal" font="default" size="100%">McClymont, Sarah A</style></author><author><style face="normal" font="default" size="100%">Hook, Paul W</style></author><author><style face="normal" font="default" size="100%">Iossifov, Ivan</style></author><author><style face="normal" font="default" size="100%">Raja, Archana</style></author><author><style face="normal" font="default" size="100%">Baker, Carl</style></author><author><style face="normal" font="default" size="100%">Hoekzema, Kendra</style></author><author><style face="normal" font="default" size="100%">Stessman, Holly A</style></author><author><style face="normal" font="default" size="100%">Zody, Michael C</style></author><author><style face="normal" font="default" size="100%">Nelson, Bradley J</style></author><author><style face="normal" font="default" size="100%">Huddleston, John</style></author><author><style face="normal" font="default" size="100%">Sandstrom, Richard</style></author><author><style face="normal" font="default" size="100%">Smith, Joshua D</style></author><author><style face="normal" font="default" size="100%">Hanna, David</style></author><author><style face="normal" font="default" size="100%">Swanson, James M</style></author><author><style face="normal" font="default" size="100%">Faustman, Elaine M</style></author><author><style face="normal" font="default" size="100%">Bamshad, Michael J</style></author><author><style face="normal" font="default" size="100%">Stamatoyannopoulos, John</style></author><author><style face="normal" font="default" size="100%">Nickerson, Deborah A</style></author><author><style face="normal" font="default" size="100%">McCallion, Andrew S</style></author><author><style face="normal" font="default" size="100%">Darnell, Robert</style></author><author><style face="normal" font="default" size="100%">Eichler, Evan E</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA.</style></title><secondary-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Am J Hum Genet</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Autistic Disorder</style></keyword><keyword><style  face="normal" font="default" size="100%">DNA</style></keyword><keyword><style  face="normal" font="default" size="100%">Exome</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Genome, Human</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Male</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Polymorphism, Single Nucleotide</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2016 Jan 07</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">98</style></volume><pages><style face="normal" font="default" size="100%">58-74</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;We performed whole-genome sequencing (WGS) of 208 genomes from 53 families affected by simplex autism. For the majority of these families, no copy-number variant (CNV) or candidate de novo gene-disruptive single-nucleotide variant (SNV) had been detected by microarray or whole-exome sequencing (WES). We integrated multiple CNV and SNV analyses and extensive experimental validation to identify additional candidate mutations in eight families. We report that compared to control individuals, probands showed a significant (p = 0.03) enrichment of de novo and private disruptive mutations within fetal CNS DNase I hypersensitive sites (i.e., putative regulatory regions). This effect was only observed within 50 kb of genes that have been previously associated with autism risk, including genes where dosage sensitivity has already been established by recurrent disruptive de novo protein-coding mutations (ARID1B, SCN2A, NR3C2, PRKCA, and DSCAM). In addition, we provide evidence of gene-disruptive CNVs (in DISC1, WNT7A, RBFOX1, and MBD5), as well as smaller de novo CNVs and exon-specific SNVs missed by exome sequencing in neurodevelopmental genes (e.g., CANX, SAE1, and PIK3CA). Our results suggest that the detection of smaller, often multiple CNVs affecting putative regulatory elements might help explain additional risk of simplex autism.&lt;/p&gt;</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><custom1><style face="normal" font="default" size="100%">https://www.ncbi.nlm.nih.gov/pubmed/26749308?dopt=Abstract</style></custom1></record></records></xml>