Conditional eQTL analysis reveals allelic heterogeneity of gene expression

Rick Jansen; Jouke-Jan Hottenga; Michel G. Nivard; Abdel Abdellaoui; Bram Laport; Eco J. de Geus; Fred A. Wright; Brenda W. J. H. Penninx; Dorret I. Boomsma

doi:10.1093/hmg/ddx043

Conditional eQTL analysis reveals allelic heterogeneity of gene expression

Rick Jansen, Jouke-Jan Hottenga, Michel G. Nivard, Abdel Abdellaoui, Bram Laport, Eco J. de Geus, Fred A. Wright, Brenda W. J. H. Penninx, Dorret I. Boomsma

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

Abstract

In recent years, multiple eQTL (expression quantitative trait loci) catalogs have become available that can help understand the functionality of complex trait-related single nucleotide polymorphisms (SNPs). In eQTL catalogs, gene expression is often strongly associated with multiple SNPs, which may reflect either one or multiple independent associations. Conditional eQTL analysis allows a distinction between dependent and independent eQTLs. We performed conditional eQTL analysis in 4,896 peripheral blood microarray gene expression samples. Our analysis showed that 35% of genes with a cis eQTL have at least two independent cis eQTLs; for several genes up to 13 independent cis eQTLs were identified. Also, 12% (671) of the independent cis eQTLs identified in conditional analyses were not significant in unconditional analyses. The number of GWAS catalog SNPs identified as eQTL in the conditional analyses increases with 24% as compared to unconditional analyses. We provide an online conditional cis eQTL mapping catalog for whole blood (https://eqtl.onderzoek.io/), which can be used to lookup eQTLs more accurately than in standard unconditional whole blood eQTL databases.

Original language	English
Pages (from-to)	1444-1451
Journal	Human Molecular Genetics
Volume	26
Issue number	8
DOIs	https://doi.org/10.1093/hmg/ddx043
Publication status	Published - 15 Apr 2017

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10.1093/hmg/ddx043

Cite this

@article{52ed72b5164f425aa6610ea3bb0965ce,

title = "Conditional eQTL analysis reveals allelic heterogeneity of gene expression",

abstract = "In recent years, multiple eQTL (expression quantitative trait loci) catalogs have become available that can help understand the functionality of complex trait-related single nucleotide polymorphisms (SNPs). In eQTL catalogs, gene expression is often strongly associated with multiple SNPs, which may reflect either one or multiple independent associations. Conditional eQTL analysis allows a distinction between dependent and independent eQTLs. We performed conditional eQTL analysis in 4,896 peripheral blood microarray gene expression samples. Our analysis showed that 35% of genes with a cis eQTL have at least two independent cis eQTLs; for several genes up to 13 independent cis eQTLs were identified. Also, 12% (671) of the independent cis eQTLs identified in conditional analyses were not significant in unconditional analyses. The number of GWAS catalog SNPs identified as eQTL in the conditional analyses increases with 24% as compared to unconditional analyses. We provide an online conditional cis eQTL mapping catalog for whole blood (https://eqtl.onderzoek.io/), which can be used to lookup eQTLs more accurately than in standard unconditional whole blood eQTL databases.",

author = "Rick Jansen and Jouke-Jan Hottenga and Nivard, {Michel G.} and Abdel Abdellaoui and Bram Laport and {de Geus}, {Eco J.} and Wright, {Fred A.} and Penninx, {Brenda W. J. H.} and Boomsma, {Dorret I.}",

year = "2017",

month = apr,

day = "15",

doi = "10.1093/hmg/ddx043",

language = "English",

volume = "26",

pages = "1444--1451",

journal = "Human Molecular Genetics",

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publisher = "Oxford University Press",

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TY - JOUR

T1 - Conditional eQTL analysis reveals allelic heterogeneity of gene expression

AU - Jansen, Rick

AU - Hottenga, Jouke-Jan

AU - Nivard, Michel G.

AU - Abdellaoui, Abdel

AU - Laport, Bram

AU - de Geus, Eco J.

AU - Wright, Fred A.

AU - Penninx, Brenda W. J. H.

AU - Boomsma, Dorret I.

PY - 2017/4/15

Y1 - 2017/4/15

N2 - In recent years, multiple eQTL (expression quantitative trait loci) catalogs have become available that can help understand the functionality of complex trait-related single nucleotide polymorphisms (SNPs). In eQTL catalogs, gene expression is often strongly associated with multiple SNPs, which may reflect either one or multiple independent associations. Conditional eQTL analysis allows a distinction between dependent and independent eQTLs. We performed conditional eQTL analysis in 4,896 peripheral blood microarray gene expression samples. Our analysis showed that 35% of genes with a cis eQTL have at least two independent cis eQTLs; for several genes up to 13 independent cis eQTLs were identified. Also, 12% (671) of the independent cis eQTLs identified in conditional analyses were not significant in unconditional analyses. The number of GWAS catalog SNPs identified as eQTL in the conditional analyses increases with 24% as compared to unconditional analyses. We provide an online conditional cis eQTL mapping catalog for whole blood (https://eqtl.onderzoek.io/), which can be used to lookup eQTLs more accurately than in standard unconditional whole blood eQTL databases.

AB - In recent years, multiple eQTL (expression quantitative trait loci) catalogs have become available that can help understand the functionality of complex trait-related single nucleotide polymorphisms (SNPs). In eQTL catalogs, gene expression is often strongly associated with multiple SNPs, which may reflect either one or multiple independent associations. Conditional eQTL analysis allows a distinction between dependent and independent eQTLs. We performed conditional eQTL analysis in 4,896 peripheral blood microarray gene expression samples. Our analysis showed that 35% of genes with a cis eQTL have at least two independent cis eQTLs; for several genes up to 13 independent cis eQTLs were identified. Also, 12% (671) of the independent cis eQTLs identified in conditional analyses were not significant in unconditional analyses. The number of GWAS catalog SNPs identified as eQTL in the conditional analyses increases with 24% as compared to unconditional analyses. We provide an online conditional cis eQTL mapping catalog for whole blood (https://eqtl.onderzoek.io/), which can be used to lookup eQTLs more accurately than in standard unconditional whole blood eQTL databases.

U2 - 10.1093/hmg/ddx043

DO - 10.1093/hmg/ddx043

M3 - Article

C2 - 28165122

VL - 26

SP - 1444

EP - 1451

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 8

ER -