The Use of Genome-Wide eQTL Associations in Lymphoblastoid Cell Lines to Identify Novel Genetic Pathways Involved in Complex Traits

被引：27

作者：

Min, Josine L. ^{[1
]}

Taylor, Jennifer M.

Richards, J. Brent ^{[2
,3
,4
]}

Watts, Tim ^{[5
]}

Pettersson, Fredrik H. ^{[1
]}

Broxholme, John

Ahmadi, Kourosh R. ^{[4
]}

Surdulescu, Gabriela L. ^{[4
]}

Lowy, Ernesto

Gieger, Christian ^{[6
]}

Newton-Cheh, Chris ^{[7
]}

Perola, Markus ^{[8
,9
]}

Soranzo, Nicole ^{[4
,10
]}

Surakka, Ida ^{[8
,9
]}

Lindgren, Cecilia M. ^{[1
]}

Ragoussis, Jiannis ^{[5
]}

Morris, Andrew P. ^{[1
]}

Cardon, Lon R. ^{[1
,11
]}

Spector, Tim D. ^{[4
]}

Zondervan, Krina T. ^{[1
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England

[2] McGill Univ, Dept Med, Montreal, PQ, Canada

[3] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[4] Kings Coll London, Twin Res & Genet Epidemiol Unit, London WC2R 2LS, England

[5] Univ Oxford, Wellcome Trust Ctr Human Genet, Genom Lab, Oxford, England

[6] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany

[7] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Broad Inst Harvard & MIT, Boston, MA USA

[8] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland

[9] Natl Inst Hlth Welf, Helsinki, Finland

[10] Wellcome Trust Sanger Inst, Cambridge, England

[11] GlaxoSmithKline, King Of Prussia, PA USA

来源：

PLOS ONE | 2011年 / 6卷 / 07期

基金：

英国惠康基金;

关键词：

COMMON VARIANTS; EXPRESSION; LOCI; RISK; NUCLEOTIDE; CONTRIBUTE; DISCOVERY; DENSITY; LINKAGE; DESIGN;

D O I：

10.1371/journal.pone.0022070

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The integrated analysis of genotypic and expression data for association with complex traits could identify novel genetic pathways involved in complex traits. We profiled 19,573 expression probes in Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) from 299 twins and correlated these with 44 quantitative traits (QTs). For 939 expressed probes correlating with more than one QT, we investigated the presence of eQTL associations in three datasets of 57 CEU HapMap founders and 86 unrelated twins. Genome-wide association analysis of these probes with 2.2 m SNPs revealed 131 potential eQTLs (1,989 eQTL SNPs) overlapping between the HapMap datasets, five of which were in cis (58 eQTL SNPs). We then tested 535 SNPs tagging the eQTL SNPs, for association with the relevant QT in 2,905 twins. We identified nine potential SNP-QT associations (P<0.01) but none significantly replicated in five large consortia of 1,097-16,129 subjects. We also failed to replicate previous reported eQTL associations with body mass index, plasma low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels derived from lymphocytes, adipose and liver tissue. Our results and additional power calculations suggest that proponents may have been overoptimistic in the power of LCLs in eQTL approaches to elucidate regulatory genetic effects on complex traits using the small datasets generated to date. Nevertheless, larger tissue-specific expression data sets relevant to specific traits are becoming available, and should enable the adoption of similar integrated analyses in the near future.

引用

页数：14

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