Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Daria V Zhernakova  1 , Patrick Deelen  1   2 , Martijn Vermaat  3 , Maarten van Iterson  4 , Michiel van Galen  3 , Wibowo Arindrarto  5 , Peter van 't Hof  5 , Hailiang Mei  5 , Freerk van Dijk  1   2 , Harm-Jan Westra  6   7   8 , Marc Jan Bonder  1 , Jeroen van Rooij  9 , Marijn Verkerk  9 , P Mila Jhamai  9 , Matthijs Moed  4 , Szymon M Kielbasa  4 , Jan Bot  10 , Irene Nooren  10 , René Pool  11 , Jenny van Dongen  11 , Jouke J Hottenga  11 , Coen D A Stehouwer  12   13 , Carla J H van der Kallen  12   13 , Casper G Schalkwijk  12   13 , Alexandra Zhernakova  1 , Yang Li  1 , Ettje F Tigchelaar  1 , Niek de Klein  1 , Marian Beekman  4 , Joris Deelen  4 , Diana van Heemst  14 , Leonard H van den Berg  15 , Albert Hofman  16 , André G Uitterlinden  9 , Marleen M J van Greevenbroek  12   13 , Jan H Veldink  15 , Dorret I Boomsma  11 , Cornelia M van Duijn  17 , Cisca Wijmenga  1 , P Eline Slagboom  4 , Morris A Swertz  1   2 , Aaron Isaacs  13   17   18 , Joyce B J van Meurs  9 , Rick Jansen  19 , Bastiaan T Heijmans  4 , Peter A C 't Hoen  3 , Lude Franke  1
Affiliations

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

Daria V Zhernakova et al. Nat Genet. 2017 Jan.

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.

PubMed Disclaimer

References

    1. N Engl J Med. 2015 Sep 3;373(10 ):895-907 - PubMed
    1. Nat Protoc. 2007;2(10):2366-82 - PubMed
    1. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 - PubMed
    1. Nat Rev Immunol. 2014 Jan;14(1):36-49 - PubMed
    1. Nat Biotechnol. 2012 Mar 07;30(3):224-6 - PubMed

Publication types

LinkOut - more resources