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

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

doi:10.1038/ng.3737

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

Daria V Zhernakova, Patrick Deelen, Martijn Vermaat, Maarten van Iterson, Michiel van Galen, Wibowo Arindrarto, Peter van 't Hof, Hailiang Mei, Freerk van Dijk, Harm-Jan Westra, Marc Jan Bonder, Jeroen van Rooij, Marijn Verkerk, P Mila Jhamai, Matthijs Moed, Szymon M Kielbasa, Jan Bot, Irene Nooren, René Pool, J. van DongenJouke J Hottenga, Coen D A Stehouwer, Carla J H van der Kallen, Casper G Schalkwijk, Alexandra Zhernakova, Yang Li, Ettje F Tigchelaar, Niek de Klein, Marian Beekman, Joris Deelen, Diana van Heemst, Leonard H van den Berg, Albert Hofman, André G Uitterlinden, Marleen J. Van Greevenbroek, Jan H Veldink, Dorret I Boomsma, Cornelia M van Duijn, Cisca Wijmenga, P. Eline Slagboom, Morris a. Swertz, Aaron Isaacs, Joyce B J van Meurs, Rick Jansen, Bastiaan T Heijmans, Peter a.C ’t Hoen, Lude Franke, Peter A.C. Hoen't

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	139-145
Number of pages	7
Journal	Nature Genetics
Volume	49
Issue number	1
Early online date	5 Dec 2016
DOIs	https://doi.org/10.1038/ng.3737
Publication status	Published - 1 Jan 2017

Keywords

Journal Article

Cohort Studies

Netherlands Twin Register (NTR)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://research.vu.nl/ws/files/299296283/ng.3737_Identification_of_context-dependent_expression_quantitative_trait_loci_in_whole_blood.pdfLicence: Article 25fa Dutch Copyright Act

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Zhernakova, D. V., Deelen, P., Vermaat, M., van Iterson, M., van Galen, M., Arindrarto, W., van 't Hof, P., Mei, H., van Dijk, F., Westra, H.-J., Bonder, M. J., van Rooij, J., Verkerk, M., Jhamai, P. M., Moed, M., Kielbasa, S. M., Bot, J., Nooren, I., Pool, R., ... Hoen't, P. A. C. (2017). Identification of context-dependent expression quantitative trait loci in whole blood. Nature Genetics, 49(1), 139-145. https://doi.org/10.1038/ng.3737

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Zhernakova, DV, Deelen, P, Vermaat, M, van Iterson, M, van Galen, M, Arindrarto, W, van 't Hof, P, Mei, H, van Dijk, F, Westra, H-J, Bonder, MJ, van Rooij, J, Verkerk, M, Jhamai, PM, Moed, M, Kielbasa, SM, Bot, J, Nooren, I, Pool, R, van Dongen, J, Hottenga, JJ, Stehouwer, CDA, van der Kallen, CJH, Schalkwijk, CG, Zhernakova, A, Li, Y, Tigchelaar, EF, de Klein, N, Beekman, M, Deelen, J, van Heemst, D, van den Berg, LH, Hofman, A, Uitterlinden, AG, Van Greevenbroek, MJ, Veldink, JH, Boomsma, DI, van Duijn, CM, Wijmenga, C, Slagboom, PE, Swertz, MA, Isaacs, A, van Meurs, JBJ, Jansen, R, Heijmans, BT, ’t Hoen, PAC, Franke, L & Hoen't, PAC 2017, 'Identification of context-dependent expression quantitative trait loci in whole blood', Nature Genetics, vol. 49, no. 1, pp. 139-145. https://doi.org/10.1038/ng.3737

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T1 - Identification of context-dependent expression quantitative trait loci in whole blood

AU - Zhernakova, Daria V

AU - Deelen, Patrick

AU - Vermaat, Martijn

AU - van Iterson, Maarten

AU - van Galen, Michiel

AU - Arindrarto, Wibowo

AU - van 't Hof, Peter

AU - Mei, Hailiang

AU - van Dijk, Freerk

AU - Westra, Harm-Jan

AU - Bonder, Marc Jan

AU - van Rooij, Jeroen

AU - Verkerk, Marijn

AU - Jhamai, P Mila

AU - Moed, Matthijs

AU - Kielbasa, Szymon M

AU - Bot, Jan

AU - Nooren, Irene

AU - Pool, René

AU - van Dongen, J.

AU - Hottenga, Jouke J

AU - Stehouwer, Coen D A

AU - van der Kallen, Carla J H

AU - Schalkwijk, Casper G

AU - Zhernakova, Alexandra

AU - Li, Yang

AU - Tigchelaar, Ettje F

AU - de Klein, Niek

AU - Beekman, Marian

AU - Deelen, Joris

AU - van Heemst, Diana

AU - van den Berg, Leonard H

AU - Hofman, Albert

AU - Uitterlinden, André G

AU - Van Greevenbroek, Marleen J.

AU - Veldink, Jan H

AU - Boomsma, Dorret I

AU - van Duijn, Cornelia M

AU - Wijmenga, Cisca

AU - Slagboom, P. Eline

AU - Swertz, Morris a.

AU - Isaacs, Aaron

AU - van Meurs, Joyce B J

AU - Jansen, Rick

AU - Heijmans, Bastiaan T

AU - ’t Hoen, Peter a.C

AU - Franke, Lude

AU - Hoen't, Peter A.C.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Journal Article

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U2 - 10.1038/ng.3737

DO - 10.1038/ng.3737

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EP - 145

JO - Nature Genetics

JF - Nature Genetics

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ER -

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

Abstract

Keywords

Cohort Studies

UN SDGs

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