title: Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets.
abstract: Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data from GWAS with data from expression quantitative trait locus (eQTL) studies to identify genes whose expression levels are associated with a complex trait because of pleiotropy. We apply the method to five human complex traits using GWAS data on up to 339,224 individuals and eQTL data on 5,311 individuals, and we prioritize 126 genes (for example, TRAF1 and ANKRD55 for rheumatoid arthritis and SNX19 and NMRAL1 for schizophrenia), of which 25 genes are new candidates; 77 genes are not the nearest annotated gene to the top associated GWAS SNP. These genes provide important leads to design future functional studies to understand the mechanism whereby DNA variation leads to complex trait variation.
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Futao
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Han
authors.initials: H
authors.lastname: Hu
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bakshi
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Robinson
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Powell
authors.affiliation: Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Victoria, Australia.|Biosciences Research Division, Department of Economic Development, Jobs, Transport and Resources, Bundoora, Victoria, Australia.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Naomi R
authors.identifier: 0000-0001-7421-3357
authors.initials: NR
authors.lastname: Wray
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, Queensland, Australia.
authors.forename: Peter M
authors.identifier: 0000-0002-2143-8760
authors.initials: PM
authors.lastname: Visscher
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|University of Queensland Diamantina Institute, Translation Research Institute, Brisbane, Queensland, Australia.
authors.forename: Jian
authors.identifier: 0000-0003-2001-2474
authors.initials: J
authors.lastname: Yang
mesh_terms: D003627:Data Interpretation, Statistical; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D058685:Genetic Pleiotropy; D005821:Genetic Techniques; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D040641:Quantitative Trait Loci; D059467:Transcriptome