Integrative Approaches for Large-scale Transcriptome-wide Association Studies

Overview

Journal Nat Genet

Specialty Genetics

Date 2016 Feb 9

PMID 26854917

Citations 1108

Authors

Alexander Gusev

Arthur Ko

Huwenbo Shi

Gaurav Bhatia

Wonil Chung

Brenda W J H Penninx

Rick Jansen

Eco J C de Geus

Dorret I Boomsma

Fred A Wright

Patrick F Sullivan

Elina Nikkola

Marcus Alvarez

Mete Civelek

Aldons J Lusis

Terho Lehtimaki

Emma Raitoharju

Mika Kahonen

Ilkka Seppala

Olli T Raitakari

Johanna Kuusisto

Markku Laakso

Alkes L Price

Paivi Pajukanta

Bogdan Pasaniuc

Affiliations

Soon will be listed here.

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 ∼ 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.

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