Format

Send to

Choose Destination
Nat Genet. 2014 May;46(5):430-7. doi: 10.1038/ng.2951. Epub 2014 Apr 13.

Heritability and genomics of gene expression in peripheral blood.

Author information

1
1] Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA. [2] Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA. [3] Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA. [4].
2
1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. [2].
3
Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA.
4
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
5
Department of Psychiatry, VU Medical Center, Amsterdam, The Netherlands.
6
1] Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA. [2] Department of Statistics, North Carolina State University, Raleigh, North Carolina, USA.
7
Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
8
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
9
Environmental and Occupational Health Sciences Institute, Rutgers University, New Brunswick, New Jersey, USA.
10
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
11
Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia, USA.
12
Department of Computer Science, University of California, Los Angeles, Los Angeles, California, USA.

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 (∼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.

PMID:
24728292
PMCID:
PMC4012342
DOI:
10.1038/ng.2951
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center