Strategies for Enriching Variant Coverage in Candidate Disease Loci on a Multiethnic Genotyping Array.
Strategies for Enriching Variant Coverage in Candidate Disease Loci on a Multiethnic Genotyping Array.
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DOI：
10.1371/journal.pone.0167758
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
PAGE Study
中科院分区：
文献类型：
--
作者：
Bien SA;Wojcik GL;Zubair N;Gignoux CR;Martin AR;Kocarnik JM;Martin LW;Buyske S;Haessler J;Walker RW;Cheng I;Graff M;Xia L;Franceschini N;Matise T;James R;Hindorff L;Le Marchand L;North KE;Haiman CA;Peters U;Loos RJ;Kooperberg CL;Bustamante CD;Kenny EE;Carlson CS;PAGE Study
研究复杂性状的遗传结构在祖先多样化的人群是必要的，以了解疾病的病因。然而，目前缺乏对美国非洲和拉丁美洲血统、西班牙裔和土著人民的遗传研究，可能会加剧许多常见疾病的现有健康差距。使用基因组学和流行病学的种群结构二期（PAGE II）研究于2013年由国家人类基因组研究所发起，旨在扩大我们对种族多样化和特征良好的研究人群中复杂性状位点的理解。为了实现这一目标，多种族基因分型阵列（MEGA）旨在通过增加代谢、心血管、肾脏、炎症、人体测量和各种生活方式特征的已知位点的变异覆盖率，大大改善精细定位和功能发现。研究临床相关突变、假定风险等位基因和已知功能变异在多个人群中的频率分布，将为了解复杂疾病的遗传结构提供重要见解，并有助于发现新的、有时是人群特异性的疾病关联。来自51650名自我认定的非洲血统（17328人）、西班牙裔/拉丁裔（22379人）、亚洲/太平洋岛民（8640人）和美洲印第安人（653人）的DNA样本，以及另外2650名南亚或欧洲血统的参与者，以及其他参考小组的DNA样本，已经通过PAGE II在MEGA上进行了基因分型。MEGA被设计为研究祖先多样性种群的新资源。在这里，我们描述了选择用于多民族人群的性状特异性内容的方法，以及如何为该内容丰富MEGA可能有助于对复杂疾病的遗传病因有更深的生物学理解。
Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA) was designed to substantially improve fine-mapping and functional discovery by increasing variant coverage across multiple ethnicities at known loci for metabolic, cardiovascular, renal, inflammatory, anthropometric, and a variety of lifestyle traits. Studying the frequency distribution of clinically relevant mutations, putative risk alleles, and known functional variants across multiple populations will provide important insight into the genetic architecture of complex diseases and facilitate the discovery of novel, sometimes population-specific, disease associations. DNA samples from 51,650 self-identified African ancestry (17,328), Hispanic/Latino (22,379), Asian/Pacific Islander (8,640), and American Indian (653) and an additional 2,650 participants of either South Asian or European ancestry, and other reference panels have been genotyped on MEGA by PAGE II. MEGA was designed as a new resource for studying ancestrally diverse populations. Here, we describe the methodology for selecting trait-specific content for use in multi-ethnic populations and how enriching MEGA for this content may contribute to deeper biological understanding of the genetic etiology of complex disease.
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DOI：
10.1038/nrg2760
发表时间：
2010-05
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1093/bioinformatics/btr043
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Haeussler M;Gerner M;Bergman CM
通讯作者：
Bergman CM
影响因子：
3.5
作者：
Griseri, Paola;Bourcier, Christine;Pages, Gilles
通讯作者：
Pages, Gilles
影响因子：
5.6
作者：
Sorlie, Paul D.;Aviles-Santa, Larissa M.;Wassertheil-Smoller, Sylvia;Kaplan, Robert C.;Daviglus, Martha L.;Giachello, Aida L.;Schneiderman, Neil;Raij, Leopoldo;Talavera, Gregory;Allison, Matthew;Lavange, Lisa;Chambless, Lloyd E.;Heiss, Gerardo
通讯作者：
Heiss, Gerardo
影响因子：
64.5
作者：
McClellan, Jon;King, Mary-Claire
通讯作者：
King, Mary-Claire