Estimating heritability and its enrichment in tissue-specific gene sets in admixed populations.
Estimating heritability and its enrichment in tissue-specific gene sets in admixed populations.
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DOI：
10.1093/hmg/ddab130
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发表时间：
2021-07-28
影响因子：
3.5
通讯作者：
Raychaudhuri S
中科院分区：
文献类型：
--
作者：
Luo Y;Li X;Wang X;Gazal S;Mercader JM;23 and Me Research Team;SIGMA Type 2 Diabetes Consortium;Neale BM;Florez JC;Auton A;Price AL;Finucane HK;Raychaudhuri S
在不同的群体中研究复杂性状的遗传是很重要的。在这里，我们介绍了协变量调整的连锁不平衡（LD）评分回归（cov-LDSC），一种估计SNP遗传力的方法（及其在同质和混合人群中的富集与汇总统计和样本内LD估计）。样本内LD可以从全基因组关联研究样本的子集中估计，使我们的方法能够有效地应用于非常大的队列。在模拟中，我们表明，未经调整的LDSC低估了10-60%的混合人群;相比之下，cov-LDSC是稳健准确的。我们将cov-LDSC应用于来自8124个个体的基因分型数据，其中大部分是来自Slim Initiative in Genomic Medicine for the Americas研究的混合血统，以及大约161 000个拉丁血统个体，47 000个非洲裔美国人血统个体和135 000个欧洲血统个体，由23andMe分类。我们估计和检测的遗传力富集在三个定量和五个二分表型，使之成为，据我们所知，最全面的遗传为基础的分析混合个人的日期。多数性状在不同群体间具有较高的一致性和一致的组织特异遗传力富集。然而，对于初潮年龄，我们观察到特定人群的遗传力估计。我们观察到不同人群中组织特异性遗传力富集的一致模式;例如，在BMI的边缘系统中，拉丁裔、非裔美国人和欧洲血统人群的每标准化注释效应量 * 分别为0.16 ± 0.04、0.28 ± 0.11和0.18 ± 0.03。我们的方法是一个强大的方法来分析遗传数据的复杂性状从混合人口。
It is important to study the genetics of complex traits in diverse populations. Here, we introduce covariate-adjusted linkage disequilibrium (LD) score regression (cov-LDSC), a method to estimate SNP-heritability ( and its enrichment in homogenous and admixed populations with summary statistics and in-sample LD estimates. In-sample LD can be estimated from a subset of the genome-wide association studies samples, allowing our method to be applied efficiently to very large cohorts. In simulations, we show that unadjusted LDSC underestimates by 10–60% in admixed populations; in contrast, cov-LDSC is robustly accurate. We apply cov-LDSC to genotyping data from 8124 individuals, mostly of admixed ancestry, from the Slim Initiative in Genomic Medicine for the Americas study, and to approximately 161 000 Latino-ancestry individuals, 47 000 African American-ancestry individuals and 135 000 European-ancestry individuals, as classified by 23andMe. We estimate and detect heritability enrichment in three quantitative and five dichotomous phenotypes, making this, to our knowledge, the most comprehensive heritability-based analysis of admixed individuals to date. Most traits have high concordance of and consistent tissue-specific heritability enrichment among different populations. However, for age at menarche, we observe population-specific heritability estimates of . We observe consistent patterns of tissue-specific heritability enrichment across populations; for example, in the limbic system for BMI, the per-standardized-annotation effect size * is 0.16 ± 0.04, 0.28 ± 0.11 and 0.18 ± 0.03 in the Latino-, African American- and European-ancestry populations, respectively. Our approach is a powerful way to analyze genetic data for complex traits from admixed populations.
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影响因子：
4.5
作者：
Gutenkunst RN;Hernandez RD;Williamson SH;Bustamante CD
通讯作者：
Bustamante CD
影响因子：
4.5
作者：
Homburger JR;Moreno-Estrada A;Gignoux CR;Nelson D;Sanchez E;Ortiz-Tello P;Pons-Estel BA;Acevedo-Vasquez E;Miranda P;Langefeld CD;Gravel S;Alarcón-Riquelme ME;Bustamante CD
通讯作者：
Bustamante CD
影响因子：
9.8
作者：
Gusev, Alexander;Lee, S. Hong;Price, Alkes L.
通讯作者：
Price, Alkes L.
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.
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew