Heritability and genomics of gene expression in peripheral blood

被引：251

作者：

Wright, Fred A. ^{[1
,2
,3
]}

Sullivan, Patrick F. ^{[4
]}

Brooks, Andrew I. ^{[5
]}

Zou, Fei ^{[6
]}

Sun, Wei ^{[6
]}

Xia, Kai ^{[6
]}

Madar, Vered ^{[6
]}

Jansen, Rick ^{[7
]}

Chung, Wonil ^{[6
]}

Zhou, Yi-Hui ^{[1
,2
]}

Abdellaoui, Abdel ^{[8
]}

Batista, Sandra ^{[9
]}

Butler, Casey ^{[9
]}

Chen, Guanhua ^{[6
]}

Chen, Ting-Huei ^{[6
]}

D'Ambrosiol, David ^{[10
]}

Gallins, Paul ^{[4
]}

Ha, Min Jin ^{[6
]}

Hottenga, Jouke Jan ^{[8
]}

Huang, Shunping

Kattenberg, Mathijs ^{[8
]}

Kochar, Jaspreet ^{[10
]}

Middeldorp, Christel M. ^{[8
]}

Qui, Ani ^{[10
]}

Shabalinn, Andrey ^{[11
]}

Tischfield, Jay ^{[5
]}

Todd, Laura ^{[4
]}

Tzeng, Jung-Ying ^{[1
,2
]}

van Grootheest, Gerard ^{[7
]}

Vink, Jacqueline M. ^{[8
]}

Wang, Qi ^{[10
]}

Wang, Wei ^{[12
]}

Wang, Weibo ^{[9
]}

Willemsen, Gonneke ^{[8
]}

Smit, Johannes H. ^{[7
]}

de Geus, Eco J. ^{[8
]}

Yin, Zhaoyu ^{[6
]}

Penninx, Brenda W. J. H. ^{[7
]}

Boomsma, Dorret I. ^{[8
]}

机构：

[1] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA

[2] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA

[3] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA

[4] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[5] Rutgers State Univ, Dept Genet, New Brunswick, NJ 08903 USA

[6] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[7] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[8] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[9] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA

[10] Rutgers State Univ, Environm & Occupat Hlth Sci Inst, New Brunswick, NJ 08903 USA

[11] Virginia Commonwealth Univ, Dept Pharmacotherapy & Outcomes Sci, Richmond, VA USA

[12] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA

来源：

NATURE GENETICS | 2014年 / 46卷 / 05期

基金：

美国国家科学基金会; 欧洲研究理事会;

关键词：

COPY NUMBER VARIATION; WIDE ASSOCIATION; LOCI; VARIANTS; IMPACT; DISEASES; DATABASE; SNPS; MAP;

D O I：

10.1038/ng.2951

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (similar to 777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.

引用

页码：430 / 437

页数：8

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