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Nat Genet. 2017 Jan;49(1):139-145. doi: 10.1038/ng.3737. Epub 2016 Dec 5.

Identification of context-dependent expression quantitative trait loci in whole blood.

Author information

1
University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.
2
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
3
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
4
Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands.
5
Sequence Analysis Support Core, Leiden University Medical Center, Leiden, the Netherlands.
6
Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
7
Partners Center for Personalized Genetic Medicine, Boston, Massachusetts, USA.
8
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
9
Department of Internal Medicine, ErasmusMC, Rotterdam, the Netherlands.
10
SURFsara, Amsterdam, the Netherlands.
11
Department of Biological Psychology, Vrije Universiteit Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
12
Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
13
School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands.
14
Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
15
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
16
Department of Epidemiology, ErasmusMC, Rotterdam, the Netherlands.
17
Genetic Epidemiology Unit, Department of Epidemiology, ErasmusMC, Rotterdam, the Netherlands.
18
Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, the Netherlands.
19
Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.

Abstract

Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease. Here we generated peripheral blood RNA-seq data from 2,116 unrelated individuals and systematically identified context-dependent eQTLs using a hypothesis-free strategy that does not require previous knowledge of the identity of the modifiers. Of the 23,060 significant cis-regulated genes (false discovery rate (FDR) ≤ 0.05), 2,743 (12%) showed context-dependent eQTL effects. The majority of these effects were influenced by cell type composition. A set of 145 cis-eQTLs depended on type I interferon signaling. Others were modulated by specific transcription factors binding to the eQTL SNPs.

PMID:
27918533
DOI:
10.1038/ng.3737
[Indexed for MEDLINE]

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