Journal
NATURE GENETICS
Volume 46, Issue 5, Pages 430-437Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2951
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Funding
- American Recovery and Reinvestment Act
- NIMH Center for Collaborative Genomics Research on Mental Disorders [U24 MH068457]
- National Institute of Mental Health
- Gillings Innovations Award
- Netherlands Study of Depression and Anxiety (NESDA)
- Netherlands Twin Register (NTR)
- Netherlands Organization for Scientific Research (MagW/ZonMW) [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20]
- Spinozapremie [56-464-14192]
- Geestkracht program [10-000-1002]
- Center for Medical Systems Biology (CMSB2)
- Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL)
- VU University EMGO+ Institute for Health and Care Research
- Neuroscience Campus Amsterdam [NBIC/BioAssist/RK (2008.024)]
- European Science Foundation [EU/QLRT-2001-01254]
- European Community's Seventh Framework Programme
- ENGAGE [HEALTH-F4-2007-201413]
- European Research Council (ERC) [230374]
- [R01 MH090936]
- [R01 GM074175]
- [P42 ES005948]
- Div Of Information & Intelligent Systems
- Direct For Computer & Info Scie & Enginr [1313606] Funding Source: National Science Foundation
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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.
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