@article{debd24d886e148b6ae55bacd0d31eb8c,
title = "Heritability and genomics of gene expression in peripheral blood",
abstract = "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 ({\^a}{\^ }1/4777) 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.",
author = "Wright, {Fred A.} and Sullivan, {Patrick F.} and Brooks, {Andrew I.} and Fei Zou and Wei Sun and Kai Xia and Vered Madar and Rick Jansen and Wonil Chung and Zhou, {Yi Hui} and Abdel Abdellaoui and Sandra Batista and Casey Butler and Guanhua Chen and Chen, {Ting Huei} and David D'Ambrosio and Paul Gallins and Ha, {Min Jin} and Hottenga, {Jouke Jan} and Shunping Huang and Mathijs Kattenberg and Jaspreet Kochar and Middeldorp, {Christel M.} and Ani Qu and Andrey Shabalin and Jay Tischfield and Laura Todd and Tzeng, {Jung Ying} and {Van Grootheest}, Gerard and Vink, {Jacqueline M.} and Qi Wang and Wei Wang and Weibo Wang and Gonneke Willemsen and Smit, {Johannes H.} and {De Geus}, {Eco J.} and Zhaoyu Yin and Penninx, {Brenda W.J.H.} and Boomsma, {Dorret I.}",
note = "Funding Information: The work described in this paper was funded by the US National Institute of Mental Health (RC2 MH089951, principal investigator P.F.S.) as part of the American Recovery and Reinvestment Act of 2009. Transport, extraction and preparation of the NTR samples were carried out under a supplement to the NIMH Center for Collaborative Genomics Research on Mental Disorders (U24 MH068457, principal investigator J.T.). We thank T. Lehner (National Institute of Mental Health) for his support. Additional analytic support was provided by grants R01 MH090936, R01 GM074175 and P42 ES005948 and by a Gillings Innovations Award. The Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands Twin Register (NTR) were funded by the Netherlands Organization for Scientific Research (MagW/ZonMW; grants 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717 and 912-100-20; Spinozapremie 56-464-14192; and Geestkracht program grant 10-000-1002), the Center for Medical Systems Biology (CMSB2; NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), the VU University EMGO+ Institute for Health and Care Research and the Neuroscience Campus Amsterdam, NBIC/BioAssist/RK (2008.024), the European Science Foundation (EU/QLRT-2001-01254), the European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413) and the European Research Council (ERC; 230374).",
year = "2014",
month = may,
doi = "10.1038/ng.2951",
language = "English",
volume = "46",
pages = "430--437",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "5",
}