Mapping the human genetic architecture of COVID-19.
Mapping the human genetic architecture of COVID-19.
复制标题
DOI：
10.1038/s41586-021-03767-x
复制
发表时间：
2021-12
期刊：
影响因子：
64.8
通讯作者：
COVID-19 Host Genetics Initiative
中科院分区：
文献类型：
--
作者：
COVID-19 Host Genetics Initiative
个体的基因构成有助于对病毒感染的易感性和反应。虽然环境、临床和社会因素对接触SARS-CoV-2的机会和新冠肺炎的严重程度有影响，但宿主遗传也可能是重要的。识别宿主特有的遗传因素可能揭示治疗相关性的生物学机制，并澄清可改变的环境风险因素与SARS-CoV-2感染和预后的因果关系。我们组成了一个全球研究人员网络，以调查人类遗传学在SARS-CoV-2感染和新冠肺炎严重程度中的作用。在这里，我们描述了三项全基因组关联荟萃分析的结果，这些分析包括来自19个国家和地区的46项研究的多达49,562名新冠肺炎患者。我们报告了与SARS-CoV-2感染或新冠肺炎严重表现相关的13个全基因组显著基因座。这些基因座中有几个与先前记载的与肺部或自身免疫性和炎症性疾病有关。它们也代表了应对感染的潜在可操作机制。孟德尔随机分析支持吸烟和体重指数在严重新冠肺炎中的因果作用，尽管不支持II型糖尿病。人类遗传学研究人员聚集在一起，优先考虑数据、结果、资源和分析框架的共享，从而使识别与新冠肺炎相关的新宿主遗传因素成为可能。这种国际合作的工作模式强调了未来在新出现的大流行中发现基因的可能性，或者实际上是任何复杂的人类疾病。一个全球性的研究网络已经形成，以调查人类遗传学在SARS-CoV-2感染和新冠肺炎严重程度中的作用；本文报告了13个基因组范围的重要基因座和潜在的可操作的感染反应机制。
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease. A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.
登录
查看更多内容
影响因子：
30.8
作者：
Fingerlin, Tasha E.;Murphy, Elissa;Zhang, Weiming;Peljto, Anna L.;Brown, Kevin K.;Steele, Mark P.;Loyd, James E.;Cosgrove, Gregory P.;Lynch, David;Groshong, Steve;Collard, Harold R.;Wolters, Paul J.;Bradford, Williamson Z.;Kossen, Karl;Seiwert, Scott D.;du Bois, Roland M.;Garcia, Christine Kim;Devine, Megan S.;Gudmundsson, Gunnar;Isaksson, Helgi J.;Kaminski, Naftali;Zhang, Yingze;Gibson, Kevin F.;Lancaster, Lisa H.;Cogan, Joy D.;Mason, Wendi R.;Maher, Toby M.;Molyneaux, Philip L.;Wells, Athol U.;Moffatt, Miriam F.;Selman, Moises;Pardo, Annie;Kim, Dong Soon;Crapo, James D.;Make, Barry J.;Regan, Elizabeth A.;Walek, Dinesha S.;Daniel, Jerry J.;Kamatani, Yoichiro;Zelenika, Diana;Smith, Keith;McKean, David;Pedersen, Brent S.;Talbert, Janet;Kidd, Raven N.;Markin, Cheryl R.;Beckman, Kenneth B.;Lathrop, Mark;Schwarz, Marvin I.;Schwartz, David A.
通讯作者：
Schwartz, David A.
影响因子：
14.9
作者：
Ghoussaini M;Mountjoy E;Carmona M;Peat G;Schmidt EM;Hercules A;Fumis L;Miranda A;Carvalho-Silva D;Buniello A;Burdett T;Hayhurst J;Baker J;Ferrer J;Gonzalez-Uriarte A;Jupp S;Karim MA;Koscielny G;Machlitt-Northen S;Malangone C;Pendlington ZM;Roncaglia P;Suveges D;Wright D;Vrousgou O;Papa E;Parkinson H;MacArthur JAL;Todd JA;Barrett JC;Schwartzentruber J;Hulcoop DG;Ochoa D;McDonagh EM;Dunham I
通讯作者：
Dunham I
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.