| Literature DB >> 27918533 |
Daria V Zhernakova1, Patrick Deelen1,2, Martijn Vermaat3, Maarten van Iterson4, Michiel van Galen3, Wibowo Arindrarto5, Peter van 't Hof5, Hailiang Mei5, Freerk van Dijk1,2, Harm-Jan Westra6,7,8, Marc Jan Bonder1, Jeroen van Rooij9, Marijn Verkerk9, P Mila Jhamai9, Matthijs Moed4, Szymon M Kielbasa4, Jan Bot10, Irene Nooren10, René Pool11, Jenny van Dongen11, Jouke J Hottenga11, Coen D A Stehouwer12,13, Carla J H van der Kallen12,13, Casper G Schalkwijk12,13, Alexandra Zhernakova1, Yang Li1, Ettje F Tigchelaar1, Niek de Klein1, Marian Beekman4, Joris Deelen4, Diana van Heemst14, Leonard H van den Berg15, Albert Hofman16, André G Uitterlinden9, Marleen M J van Greevenbroek12,13, Jan H Veldink15, Dorret I Boomsma11, Cornelia M van Duijn17, Cisca Wijmenga1, P Eline Slagboom4, Morris A Swertz1,2, Aaron Isaacs13,17,18, Joyce B J van Meurs9, Rick Jansen19, Bastiaan T Heijmans4, Peter A C 't Hoen3, Lude Franke1.
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.Mesh：
Substances：
Year: 2016 PMID： 27918533 DOI： 10.1038/ng.3737
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330