TY - JOUR T1 - Integrative approaches for large-scale transcriptome-wide association studies JF - bioRxiv DO - 10.1101/024083 SP - 024083 AU - Alexander Gusev AU - Arthur Ko AU - Huwenbo Shi AU - Gaurav Bhatia AU - Wonil Chung AU - Brenda W J H Penninx AU - Rick Jansen AU - Eco JC de Geus AU - Dorret I Boomsma AU - Fred A Wright AU - Patrick F Sullivan AU - Elina Nikkola AU - Marcus Alvarez AU - Mete Civelek AU - Aldonis J. Lusis AU - Terho Lehtimäki AU - Emma Raitoharju AU - Mika Kähönen AU - Ilkka Seppälä AU - Olli T. Raitakari AU - Johanna Kuusisto AU - Markku Laakso AU - Alkes L. Price AU - Päivi Pajukanta AU - Bogdan Pasaniuc Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/08/10/024083.abstract N2 - Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance levels of one or multiple proteins. In this work we introduce a powerful strategy that integrates gene expression measurements with large-scale genome-wide association data to identify genes whose cis-regulated expression is associated to complex traits. We use a relatively small reference panel of individuals for which both genetic variation and gene expression have been measured to impute gene expression into large cohorts of individuals and identify expression-trait associations. We extend our methods to allow for indirect imputation of the expression-trait association from summary association statistics of large-scale GWAS1-3. We applied our approaches to expression data from blood and adipose tissue measured in ∼3,000 individuals overall. We then imputed gene expression into GWAS data from over 900,000 phenotype measurements4-6 to identify 69 novel genes significantly associated to obesity-related traits (BMI, lipids, and height). Many of the novel genes were associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Overall our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits. ER -