A1 Refereed original research article in a scientific journal

Integrative approaches for large-scale transcriptome-wide association studies




AuthorsGusev 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

PublisherNATURE PUBLISHING GROUP

Publication year2016

JournalNature Genetics

Journal name in sourceNATURE GENETICS

Journal acronymNAT GENET

Volume48

Issue3

First page 245

Last page252

Number of pages8

ISSN1061-4036

DOIhttps://doi.org/10.1038/ng.3506


Abstract

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.




Last updated on 2024-26-11 at 20:29