Effects of cis and trans genetic ancestry on gene expression in African Americans.
Effects of cis and trans genetic ancestry on gene expression in African Americans.
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DOI：
10.1371/journal.pgen.1000294
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发表时间：
2008-12
期刊：
影响因子：
4.5
通讯作者：
Spielman RS
中科院分区：
文献类型：
--
作者：
Price AL;Patterson N;Hancks DC;Myers S;Reich D;Cheung VG;Spielman RS
基因表达的变异是人类表型变异的一个基本方面。最近的几项研究分析了不同大陆血统人群的基因表达水平，并报告了大量基因的人群差异。然而，这些差异很大程度上可能是由于非遗传（例如环境）影响造成的。在这里，我们分析了非裔美国人细胞系中的基因表达水平，该细胞系与之前分析的细胞系不同，因为该群体中的个体继承了两个大陆血统的不同比例。我们首先将非裔美国人个体的基因表达水平与其欧洲血统的全基因组比例联系起来。这些结果提供了强有力的证据，证明遗传因素对欧洲和非洲人群之间的表达差异有贡献，验证了之前的发现。其次，我们推断基因组中每个位置的本地祖先（0、1 或 2 条欧洲染色体），并研究接近表达基因的祖先（顺式）与基因组其他地方的祖先（反式）的影响。这两种效应都非常显着，我们估计人类基因表达中所有可遗传变异的 12±3% 是由顺式变异引起的。基因表达的变异是人类表型变异的一个基本方面，了解这种变异如何在人群中分配是一个重要的目标。先前的研究比较了不同人群之间的基因表达水平，但尚不清楚观察到的差异是否具有遗传或非遗传基础。混合人群，例如非裔美国人，为这个问题提供了一个解决方案，因为个体的欧洲血统比例各不相同，而对单一人群的分析则最大限度地减少了非遗传因素。在这里，我们表明不同血统比例的非裔美国人之间的基因表达差异验证了欧洲和非洲人群之间的基因表达差异。此外，通过区分非洲裔美国人在被分析表达的基因位置（顺式）和远端位置（反式）的祖先，我们可以利用祖先效应来量化顺式和反式调节对人类基因表达的相对贡献。我们估计人类基因表达中所有可遗传变异的 12±3% 是由顺式变异引起的。
Variation in gene expression is a fundamental aspect of human phenotypic variation. Several recent studies have analyzed gene expression levels in populations of different continental ancestry and reported population differences at a large number of genes. However, these differences could largely be due to non-genetic (e.g., environmental) effects. Here, we analyze gene expression levels in African American cell lines, which differ from previously analyzed cell lines in that individuals from this population inherit variable proportions of two continental ancestries. We first relate gene expression levels in individual African Americans to their genome-wide proportion of European ancestry. The results provide strong evidence of a genetic contribution to expression differences between European and African populations, validating previous findings. Second, we infer local ancestry (0, 1, or 2 European chromosomes) at each location in the genome and investigate the effects of ancestry proximal to the expressed gene (cis) versus ancestry elsewhere in the genome (trans). Both effects are highly significant, and we estimate that 12±3% of all heritable variation in human gene expression is due to cis variants. Variation in gene expression is a fundamental aspect of human phenotypic variation, and understanding how this variation is apportioned among human populations is an important aim. Previous studies have compared gene expression levels between distinct populations, but it is unclear whether the differences that were observed have a genetic or nongenetic basis. Admixed populations, such as African Americans, offer a solution to this problem because individuals vary in their proportion of European ancestry while the analysis of a single population minimizes nongenetic factors. Here, we show that differences in gene expression among African Americans of different ancestry proportions validate gene expression differences between European and African populations. Furthermore, by drawing a distinction between an African American individual's ancestry at the location of a gene whose expression is being analyzed (cis) versus at distal locations (trans), we can use ancestry effects to quantify the relative contributions of cis and trans regulation to human gene expression. We estimate that 12±3% of all heritable variation in human gene expression is due to cis variants.
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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
影响因子：
9.8
作者：
Schadt EE;Molony C;Chudin E;Hao K;Yang X;Lum PY;Kasarskis A;Zhang B;Wang S;Suver C;Zhu J;Millstein J;Sieberts S;Lamb J;GuhaThakurta D;Derry J;Storey JD;Avila-Campillo I;Kruger MJ;Johnson JM;Rohl CA;van Nas A;Mehrabian M;Drake TA;Lusis AJ;Smith RC;Guengerich FP;Strom SC;Schuetz E;Rushmore TH;Ulrich R
通讯作者：
Ulrich R
影响因子：
10.7
作者：
Osada, Naoki;Kohn, Michael H.;Wu, Chung-I
通讯作者：
Wu, Chung-I
影响因子：
30.8
作者：
Spielman, Richard S.;Bastone, Laurel A.;Cheung, Vivian G.
通讯作者：
Cheung, Vivian G.
影响因子：
30.8
作者：
Goering, Harald H. H.;Curran, Joanne E.;Blangero, John
通讯作者：
Blangero, John