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

Dania 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; Rene Pool; Jenny 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; Andre G. Uitterlinden; Marleen M. 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

doi:10.1038/ng.3737

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

Dania 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, Rene Pool, Jenny 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, Andre G. Uitterlinden, Marleen M. 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^*

^*Corresponding author for this work

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Abstract

Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology1,2. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations(3-6). 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(7-17). 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)

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

Keywords

GENE-EXPRESSION
DISEASE ASSOCIATIONS
HUMAN NEUTROPHILS
CELL
GENOME
VARIANTS
OBESITY
ENRICHMENT
INFECTION
ALLELES

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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., ... Franke, L. (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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abstract = "Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology1,2. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations(3-6). 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(7-17). 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)",

keywords = "GENE-EXPRESSION, DISEASE ASSOCIATIONS, HUMAN NEUTROPHILS, CELL, GENOME, VARIANTS, OBESITY, ENRICHMENT, INFECTION, ALLELES",

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

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doi = "10.1038/ng.3737",

language = "English",

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journal = "Nature Genetics",

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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, MMJ, 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 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

TY - JOUR

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

AU - Zhernakova, Dania 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, Rene

AU - van Dongen, Jenny

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, Andre G.

AU - van Greevenbroek, Marleen M. 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

PY - 2017/1

Y1 - 2017/1

N2 - Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology1,2. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations(3-6). 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(7-17). 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)

AB - Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology1,2. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations(3-6). 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(7-17). 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)

KW - GENE-EXPRESSION

KW - DISEASE ASSOCIATIONS

KW - HUMAN NEUTROPHILS

KW - CELL

KW - GENOME

KW - VARIANTS

KW - OBESITY

KW - ENRICHMENT

KW - INFECTION

KW - ALLELES

U2 - 10.1038/ng.3737

DO - 10.1038/ng.3737

M3 - Article

C2 - 27918533

SN - 1061-4036

VL - 49

SP - 139

EP - 145

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -