journal
https://read.qxmd.com/read/38641645/author-correction-new-genetic-signals-for-lung-function-highlight-pathways-and-chronic-obstructive-pulmonary-disease-associations-across-multiple-ancestries
#1
Nick Shrine, Anna L Guyatt, A Mesut Erzurumluoglu, Victoria E Jackson, Brian D Hobbs, Carl A Melbourne, Chiara Batini, Katherine A Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola F Reeve, Ma'en Obeidat, Jing Hua Zhao, Matthias Wielscher, Stefan Weiss, Katherine A Kentistou, James P Cook, Benjamin B Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E Harris, Jonathan Marten, Stefan Enroth, Shona M Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Richard J Allen, Per S Bakke, Terri H Beaty, Eugene R Bleecker, Yohan Bossé, Corry-Anke Brandsma, Zhengming Chen, James D Crapo, John Danesh, Dawn L DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna L Hansell, Ke Hao, Joshua D Hoffman, John E Hokanson, Georg Homuth, Peter K Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nicholas Locantore, Jian'an Luan, Anubha Mahajan, Joseph C Maranville, Alison Murray, David C Nickle, Richard Packer, Margaret M Parker, Megan L Paynton, David J Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don D Sin, Blair H Smith, María Soler Artigas, David Sparrow, Ruth Tal-Singer, Paul R H J Timmers, Maarten Van den Berge, John C Whittaker, Prescott G Woodruff, Laura M Yerges-Armstrong, Olga G Troyanskaya, Olli T Raitakari, Mika Kähönen, Ozren Polašek, Ulf Gyllensten, Igor Rudan, Ian J Deary, Nicole M Probst-Hensch, Holger Schulz, Alan L James, James F Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nick Wareham, Edwin K Silverman, Caroline Hayward, Andrew P Morris, Adam S Butterworth, Robert A Scott, Robin G Walters, Deborah A Meyers, Michael H Cho, David P Strachan, Ian P Hall, Martin D Tobin, Louise V Wain
No abstract text is available yet for this article.
April 19, 2024: Nature Genetics
https://read.qxmd.com/read/38641644/analysis-of-blood-methylation-quantitative-trait-loci-in-east-asians-reveals-ancestry-specific-impacts-on-complex-traits
#2
JOURNAL ARTICLE
Qianqian Peng, Xinxuan Liu, Wenran Li, Han Jing, Jiarui Li, Xingjian Gao, Qi Luo, Charles E Breeze, Siyu Pan, Qiwen Zheng, Guochao Li, Jiaqiang Qian, Liyun Yuan, Na Yuan, Chenglong You, Siyuan Du, Yuanting Zheng, Ziyu Yuan, Jingze Tan, Peilin Jia, Jiucun Wang, Guoqing Zhang, Xianping Lu, Leming Shi, Shicheng Guo, Yun Liu, Ting Ni, Bo Wen, Changqing Zeng, Li Jin, Andrew E Teschendorff, Fan Liu, Sijia Wang
Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height...
April 19, 2024: Nature Genetics
https://read.qxmd.com/read/38637618/constants-and-variations-in-69-diverse-genomes-of-arabidopsis-thaliana
#3
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
April 18, 2024: Nature Genetics
https://read.qxmd.com/read/38637617/genome-wide-association-analyses-identify-95-risk-loci-and-provide-insights-into-the-neurobiology-of-post-traumatic-stress-disorder
#4
JOURNAL ARTICLE
Caroline M Nievergelt, Adam X Maihofer, Elizabeth G Atkinson, Chia-Yen Chen, Karmel W Choi, Jonathan R I Coleman, Nikolaos P Daskalakis, Laramie E Duncan, Renato Polimanti, Cindy Aaronson, Ananda B Amstadter, Soren B Andersen, Ole A Andreassen, Paul A Arbisi, Allison E Ashley-Koch, S Bryn Austin, Esmina Avdibegoviç, Dragan Babić, Silviu-Alin Bacanu, Dewleen G Baker, Anthony Batzler, Jean C Beckham, Sintia Belangero, Corina Benjet, Carisa Bergner, Linda M Bierer, Joanna M Biernacka, Laura J Bierut, Jonathan I Bisson, Marco P Boks, Elizabeth A Bolger, Amber Brandolino, Gerome Breen, Rodrigo Affonseca Bressan, Richard A Bryant, Angela C Bustamante, Jonas Bybjerg-Grauholm, Marie Bækvad-Hansen, Anders D Børglum, Sigrid Børte, Leah Cahn, Joseph R Calabrese, Jose Miguel Caldas-de-Almeida, Chris Chatzinakos, Sheraz Cheema, Sean A P Clouston, Lucía Colodro-Conde, Brandon J Coombes, Carlos S Cruz-Fuentes, Anders M Dale, Shareefa Dalvie, Lea K Davis, Jürgen Deckert, Douglas L Delahanty, Michelle F Dennis, Frank Desarnaud, Christopher P DiPietro, Seth G Disner, Anna R Docherty, Katharina Domschke, Grete Dyb, Alma Džubur Kulenović, Howard J Edenberg, Alexandra Evans, Chiara Fabbri, Negar Fani, Lindsay A Farrer, Adriana Feder, Norah C Feeny, Janine D Flory, David Forbes, Carol E Franz, Sandro Galea, Melanie E Garrett, Bizu Gelaye, Joel Gelernter, Elbert Geuze, Charles F Gillespie, Slavina B Goleva, Scott D Gordon, Aferdita Goçi, Lana Ruvolo Grasser, Camila Guindalini, Magali Haas, Saskia Hagenaars, Michael A Hauser, Andrew C Heath, Sian M J Hemmings, Victor Hesselbrock, Ian B Hickie, Kelleigh Hogan, David Michael Hougaard, Hailiang Huang, Laura M Huckins, Kristian Hveem, Miro Jakovljević, Arash Javanbakht, Gregory D Jenkins, Jessica Johnson, Ian Jones, Tanja Jovanovic, Karen-Inge Karstoft, Milissa L Kaufman, James L Kennedy, Ronald C Kessler, Alaptagin Khan, Nathan A Kimbrel, Anthony P King, Nastassja Koen, Roman Kotov, Henry R Kranzler, Kristi Krebs, William S Kremen, Pei-Fen Kuan, Bruce R Lawford, Lauren A M Lebois, Kelli Lehto, Daniel F Levey, Catrin Lewis, Israel Liberzon, Sarah D Linnstaedt, Mark W Logue, Adriana Lori, Yi Lu, Benjamin J Luft, Michelle K Lupton, Jurjen J Luykx, Iouri Makotkine, Jessica L Maples-Keller, Shelby Marchese, Charles Marmar, Nicholas G Martin, Gabriela A Martínez-Levy, Kerrie McAloney, Alexander McFarlane, Katie A McLaughlin, Samuel A McLean, Sarah E Medland, Divya Mehta, Jacquelyn Meyers, Vasiliki Michopoulos, Elizabeth A Mikita, Lili Milani, William Milberg, Mark W Miller, Rajendra A Morey, Charles Phillip Morris, Ole Mors, Preben Bo Mortensen, Mary S Mufford, Elliot C Nelson, Merete Nordentoft, Sonya B Norman, Nicole R Nugent, Meaghan O'Donnell, Holly K Orcutt, Pedro M Pan, Matthew S Panizzon, Gita A Pathak, Edward S Peters, Alan L Peterson, Matthew Peverill, Robert H Pietrzak, Melissa A Polusny, Bernice Porjesz, Abigail Powers, Xue-Jun Qin, Andrew Ratanatharathorn, Victoria B Risbrough, Andrea L Roberts, Alex O Rothbaum, Barbara O Rothbaum, Peter Roy-Byrne, Kenneth J Ruggiero, Ariane Rung, Heiko Runz, Bart P F Rutten, Stacey Saenz de Viteri, Giovanni Abrahão Salum, Laura Sampson, Sixto E Sanchez, Marcos Santoro, Carina Seah, Soraya Seedat, Julia S Seng, Andrey Shabalin, Christina M Sheerin, Derrick Silove, Alicia K Smith, Jordan W Smoller, Scott R Sponheim, Dan J Stein, Synne Stensland, Jennifer S Stevens, Jennifer A Sumner, Martin H Teicher, Wesley K Thompson, Arun K Tiwari, Edward Trapido, Monica Uddin, Robert J Ursano, Unnur Valdimarsdóttir, Miranda Van Hooff, Eric Vermetten, Christiaan H Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Monika Waszczuk, Heike Weber, Frank R Wendt, Thomas Werge, Michelle A Williams, Douglas E Williamson, Bendik S Winsvold, Sherry Winternitz, Christiane Wolf, Erika J Wolf, Yan Xia, Ying Xiong, Rachel Yehuda, Keith A Young, Ross McD Young, Clement C Zai, Gwyneth C Zai, Mark Zervas, Hongyu Zhao, Lori A Zoellner, John-Anker Zwart, Terri deRoon-Cassini, Sanne J H van Rooij, Leigh L van den Heuvel, Murray B Stein, Kerry J Ressler, Karestan C Koenen
Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new)...
April 18, 2024: Nature Genetics
https://read.qxmd.com/read/38637616/genetic-modifiers-of-rare-variants-in-monogenic-developmental-disorder-loci
#5
JOURNAL ARTICLE
Rebecca Kingdom, Robin N Beaumont, Andrew R Wood, Michael N Weedon, Caroline F Wright
Rare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DDs) and have also been shown to cause milder subclinical phenotypes in population cohorts. Here, we show that carrying multiple (2-5) rare damaging variants across 599 dominant DD genes has an additive adverse effect on numerous cognitive and socioeconomic traits in UK Biobank, which can be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Phenotypic deviators from expected EA-PGS could be partly explained by the enrichment or depletion of rare DD variants...
April 18, 2024: Nature Genetics
https://read.qxmd.com/read/38632349/integrative-common-and-rare-variant-analyses-provide-insights-into-the-genetic-architecture-of-liver-cirrhosis
#6
JOURNAL ARTICLE
Jonas Ghouse, Gardar Sveinbjörnsson, Marijana Vujkovic, Anne-Sofie Seidelin, Helene Gellert-Kristensen, Gustav Ahlberg, Vinicius Tragante, Søren A Rand, Joseph Brancale, Silvia Vilarinho, Pia Rengtved Lundegaard, Erik Sørensen, Christian Erikstrup, Mie Topholm Bruun, Bitten Aagaard Jensen, Søren Brunak, Karina Banasik, Henrik Ullum, Niek Verweij, Luca Lotta, Aris Baras, Tooraj Mirshahi, David J Carey, David E Kaplan, Julie Lynch, Timothy Morgan, Tae-Hwi Schwantes-An, Daniel R Dochtermann, Saiju Pyarajan, Philip S Tsao, Triin Laisk, Reedik Mägi, Julia Kozlitina, Anne Tybjærg-Hansen, David Jones, Kirk U Knowlton, Lincoln Nadauld, Egil Ferkingstad, Einar S Björnsson, Magnus O Ulfarsson, Árni Sturluson, Patrick Sulem, Ole B Pedersen, Sisse R Ostrowski, Daniel F Gudbjartsson, Kari Stefansson, Morten Salling Olesen, Kyong-Mi Chang, Hilma Holm, Henning Bundgaard, Stefan Stender
We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism...
April 17, 2024: Nature Genetics
https://read.qxmd.com/read/38627598/a-spatiotemporal-atlas-of-mouse-liver-homeostasis-and-regeneration
#7
JOURNAL ARTICLE
Jiangshan Xu, Pengcheng Guo, Shijie Hao, Shuncheng Shangguan, Quan Shi, Giacomo Volpe, Keke Huang, Jing Zuo, Juan An, Yue Yuan, Mengnan Cheng, Qiuting Deng, Xiao Zhang, Guangyao Lai, Haitao Nan, Baihua Wu, Xinyi Shentu, Liang Wu, Xiaoyu Wei, Yujia Jiang, Xin Huang, Fengyu Pan, Yumo Song, Ronghai Li, Zhifeng Wang, Chuanyu Liu, Shiping Liu, Yuxiang Li, Tao Yang, Zhicheng Xu, Wensi Du, Ling Li, Tanveer Ahmed, Kai You, Zhen Dai, Li Li, Baoming Qin, Yinxiong Li, Liangxue Lai, Dajiang Qin, Junling Chen, Rong Fan, Yongyin Li, Jinlin Hou, Michael Ott, Amar Deep Sharma, Tobias Cantz, Axel Schambach, Karsten Kristiansen, Andrew P Hutchins, Berthold Göttgens, Patrick H Maxwell, Lijian Hui, Xun Xu, Longqi Liu, Ao Chen, Yiwei Lai, Miguel A Esteban
The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale...
April 16, 2024: Nature Genetics
https://read.qxmd.com/read/38627597/single-mitosis-dissection-of-acute-and-chronic-dna-mutagenesis-and-repair
#8
JOURNAL ARTICLE
Paul Adrian Ginno, Helena Borgers, Christina Ernst, Anja Schneider, Mikaela Behm, Sarah J Aitken, Martin S Taylor, Duncan T Odom
How chronic mutational processes and punctuated bursts of DNA damage drive evolution of the cancer genome is poorly understood. Here, we demonstrate a strategy to disentangle and quantify distinct mechanisms underlying genome evolution in single cells, during single mitoses and at single-strand resolution. To distinguish between chronic (reactive oxygen species (ROS)) and acute (ultraviolet light (UV)) mutagenesis, we microfluidically separate pairs of sister cells from the first mitosis following burst UV damage...
April 16, 2024: Nature Genetics
https://read.qxmd.com/read/38627596/a-spatiotemporal-atlas-of-cholestatic-injury-and-repair-in-mice
#9
JOURNAL ARTICLE
Baihua Wu, Xinyi Shentu, Haitao Nan, Pengcheng Guo, Shijie Hao, Jiangshan Xu, Shuncheng Shangguan, Lei Cui, Jin Cen, Qiuting Deng, Yan Wu, Chang Liu, Yumo Song, Xiumei Lin, Zhifeng Wang, Yue Yuan, Wen Ma, Ronghai Li, Yikang Li, Qiwei Qian, Wensi Du, Tingting Lai, Tao Yang, Chuanyu Liu, Xiong Ma, Ao Chen, Xun Xu, Yiwei Lai, Longqi Liu, Miguel A Esteban, Lijian Hui
Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response. Cholangiocytes express genes related to recruitment and differentiation of lipid-associated macrophages, which generate feedback signals enhancing ductular reaction...
April 16, 2024: Nature Genetics
https://read.qxmd.com/read/38605175/a-pan-genome-of-69-arabidopsis-thaliana-accessions-reveals-a-conserved-genome-structure-throughout-the-global-species-range
#10
JOURNAL ARTICLE
Qichao Lian, Bruno Huettel, Birgit Walkemeier, Baptiste Mayjonade, Céline Lopez-Roques, Lisa Gil, Fabrice Roux, Korbinian Schneeberger, Raphael Mercier
Although originally primarily a system for functional biology, Arabidopsis thaliana has, owing to its broad geographical distribution and adaptation to diverse environments, developed into a powerful model in population genomics. Here we present chromosome-level genome assemblies of 69 accessions from a global species range. We found that genomic colinearity is very conserved, even among geographically and genetically distant accessions. Along chromosome arms, megabase-scale rearrangements are rare and typically present only in a single accession...
April 11, 2024: Nature Genetics
https://read.qxmd.com/read/38594305/tissue-specific-enhancer-gene-maps-from-multimodal-single-cell-data-identify-causal-disease-alleles
#11
JOURNAL ARTICLE
Saori Sakaue, Kathryn Weinand, Shakson Isaac, Kushal K Dey, Karthik Jagadeesh, Masahiro Kanai, Gerald F M Watts, Zhu Zhu, Michael B Brenner, Andrew McDavid, Laura T Donlin, Kevin Wei, Alkes L Price, Soumya Raychaudhuri
Translating genome-wide association study (GWAS) loci into causal variants and genes requires accurate cell-type-specific enhancer-gene maps from disease-relevant tissues. Building enhancer-gene maps is essential but challenging with current experimental methods in primary human tissues. Here we developed a nonparametric statistical method, SCENT (single-cell enhancer target gene mapping), that models association between enhancer chromatin accessibility and gene expression in single-cell or nucleus multimodal RNA sequencing and ATAC sequencing data...
April 9, 2024: Nature Genetics
https://read.qxmd.com/read/38575728/protein-truncating-variants-in-bsn-are-associated-with-severe-adult-onset-obesity-type-2-diabetes-and-fatty-liver-disease
#12
JOURNAL ARTICLE
Yajie Zhao, Maria Chukanova, Katherine A Kentistou, Zammy Fairhurst-Hunter, Anna Maria Siegert, Raina Y Jia, Georgina K C Dowsett, Eugene J Gardner, Katherine Lawler, Felix R Day, Lena R Kaisinger, Yi-Chun Loraine Tung, Brian Yee Hong Lam, Hsiao-Jou Cortina Chen, Quanli Wang, Jaime Berumen-Campos, Pablo Kuri-Morales, Roberto Tapia-Conyer, Jesus Alegre-Diaz, Inês Barroso, Jonathan Emberson, Jason M Torres, Rory Collins, Danish Saleheen, Katherine R Smith, Dirk S Paul, Florian Merkle, I Sadaf Farooqi, Nick J Wareham, Slavé Petrovski, Stephen O'Rahilly, Ken K Ong, Giles S H Yeo, John R B Perry
Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity...
April 4, 2024: Nature Genetics
https://read.qxmd.com/read/38570662/identifying-regulatory-loci-across-38-lung-cell-types
#13
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
April 3, 2024: Nature Genetics
https://read.qxmd.com/read/38565644/proteogenomic-insights-into-early-onset-endometrioid-endometrial-carcinoma-predictors-for-fertility-sparing-therapy-response
#14
JOURNAL ARTICLE
Zhe Hu, Zimeng Wu, Wei Liu, Yan Ning, Jingbo Liu, Wencheng Ding, Junpeng Fan, Shuyan Cai, Qinlan Li, Wenting Li, Xiaohang Yang, Yingyu Dou, Wei Wang, Wenju Peng, Funian Lu, Xucui Zhuang, Tianyu Qin, Xiaoyan Kang, Chenzhao Feng, Zhiying Xu, Qiaoying Lv, Qian Wang, Chao Wang, Xinyu Wang, Zhiqi Wang, Jianliu Wang, Jie Jiang, Beibei Wang, Gordon B Mills, Ding Ma, Qinglei Gao, Kezhen Li, Gang Chen, Xiaojun Chen, Chaoyang Sun
Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways...
April 2, 2024: Nature Genetics
https://read.qxmd.com/read/38553554/mapping-single-cell-gene-expression-in-the-healthy-human-breast
#15
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
March 29, 2024: Nature Genetics
https://read.qxmd.com/read/38553553/comprehensive-whole-genome-sequence-analyses-provide-insights-into-the-genomic-architecture-of-cerebral-palsy
#16
JOURNAL ARTICLE
Darcy L Fehlings, Mehdi Zarrei, Worrawat Engchuan, Neal Sondheimer, Bhooma Thiruvahindrapuram, Jeffrey R MacDonald, Edward J Higginbotham, Ritesh Thapa, Tarannum Behlim, Sabrina Aimola, Lauren Switzer, Pamela Ng, John Wei, Prakroothi S Danthi, Giovanna Pellecchia, Sylvia Lamoureux, Karen Ho, Sergio L Pereira, Jill de Rijke, Wilson W L Sung, Alireza Mowjoodi, Jennifer L Howe, Thomas Nalpathamkalam, Roozbeh Manshaei, Siavash Ghaffari, Joseph Whitney, Rohan V Patel, Omar Hamdan, Rulan Shaath, Brett Trost, Shannon Knights, Dawa Samdup, Anna McCormick, Carolyn Hunt, Adam Kirton, Anne Kawamura, Ronit Mesterman, Jan Willem Gorter, Nomazulu Dlamini, Daniele Merico, Murto Hilali, Kyle Hirschfeld, Kritika Grover, Nelson X Bautista, Kara Han, Christian R Marshall, Ryan K C Yuen, Padmaja Subbarao, Meghan B Azad, Stuart E Turvey, Piush Mandhane, Theo J Moraes, Elinor Simons, George Maxwell, Michael Shevell, Gregory Costain, Jacques L Michaud, Fadi F Hamdan, Julie Gauthier, Kevin Uguen, Dimitri J Stavropoulos, Richard F Wintle, Maryam Oskoui, Stephen W Scherer
We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.7%) as having variants of uncertain significance. Multiple classes of P/LP variants included single-nucleotide variants (SNVs)/indels (6.7%), copy number variations (3.4%) and mitochondrial mutations (1.5%). The COL4A1 gene had the most P/LP SNVs. We also analyzed two pediatric control cohorts (n = 203 trios and n = 89 sib-pair families) to provide a baseline for de novo mutation rates and genetic burden analyses, the latter of which demonstrated associations between de novo deleterious variants and genes related to the nervous system...
March 29, 2024: Nature Genetics
https://read.qxmd.com/read/38548990/cell-type-specific-and-disease-associated-expression-quantitative-trait-loci-in-the-human-lung
#17
JOURNAL ARTICLE
Heini M Natri, Christina B Del Azodi, Lance Peter, Chase J Taylor, Sagrika Chugh, Robert Kendle, Mei-I Chung, David K Flaherty, Brittany K Matlock, Carla L Calvi, Timothy S Blackwell, Lorraine B Ware, Matthew Bacchetta, Rajat Walia, Ciara M Shaver, Jonathan A Kropski, Davis J McCarthy, Nicholas E Banovich
Common genetic variants confer substantial risk for chronic lung diseases, including pulmonary fibrosis. Defining the genetic control of gene expression in a cell-type-specific and context-dependent manner is critical for understanding the mechanisms through which genetic variation influences complex traits and disease pathobiology. To this end, we performed single-cell RNA sequencing of lung tissue from 66 individuals with pulmonary fibrosis and 48 unaffected donors. Using a pseudobulk approach, we mapped expression quantitative trait loci (eQTLs) across 38 cell types, observing both shared and cell-type-specific regulatory effects...
March 28, 2024: Nature Genetics
https://read.qxmd.com/read/38548989/protein-altering-variants-at-copy-number-variable-regions-influence-diverse-human-phenotypes
#18
JOURNAL ARTICLE
Margaux L A Hujoel, Robert E Handsaker, Maxwell A Sherman, Nolan Kamitaki, Alison R Barton, Ronen E Mukamel, Chikashi Terao, Steven A McCarroll, Po-Ru Loh
Copy number variants (CNVs) are among the largest genetic variants, yet CNVs have not been effectively ascertained in most genetic association studies. Here we ascertained protein-altering CNVs from UK Biobank whole-exome sequencing data (n = 468,570) using haplotype-informed methods capable of detecting subexonic CNVs and variation within segmental duplications. Incorporating CNVs into analyses of rare variants predicted to cause gene loss of function (LOF) identified 100 associations of predicted LOF variants with 41 quantitative traits...
March 28, 2024: Nature Genetics
https://read.qxmd.com/read/38548988/a-single-cell-atlas-enables-mapping-of-homeostatic-cellular-shifts-in-the-adult-human-breast
#19
JOURNAL ARTICLE
Austin D Reed, Sara Pensa, Adi Steif, Jack Stenning, Daniel J Kunz, Linsey J Porter, Kui Hua, Peng He, Alecia-Jane Twigger, Abigail J Q Siu, Katarzyna Kania, Rachel Barrow-McGee, Iain Goulding, Jennifer J Gomm, Valerie Speirs, J Louise Jones, John C Marioni, Walid T Khaled
Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways...
March 28, 2024: Nature Genetics
https://read.qxmd.com/read/38528243/exit-from-totipotency-is-controlled-by-duxbl-in-mice
#20
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
March 25, 2024: Nature Genetics
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