A1 Refereed original research article in a scientific journal
Integrative approaches for large-scale transcriptome-wide association studies
Authors: Gusev A, Ko A, Shi H, Bhatia G, Chung W, Penninx BWJH, Jansen R, de Geus EJC, Boomsma DI, Wright FA, Sullivan PF, Nikkola E, Alvarez M, Civelek M, Lusis AJ, Lehtimaki T, Raitoharju E, Kahonen M, Seppala I, Raitakari OT, Kuusisto J, Laakso M, Price AL, Pajukanta P, Pasaniuc B
Publisher: NATURE PUBLISHING GROUP
Publication year: 2016
Journal: Nature Genetics
Journal name in source: NATURE GENETICS
Journal acronym: NAT GENET
Volume: 48
Issue: 3
First page : 245
Last page: 252
Number of pages: 8
ISSN: 1061-4036
DOI: https://doi.org/10.1038/ng.3506
Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in similar to 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.