TY - JOUR T1 - Integrating tissue specific mechanisms into GWAS summary results JF - bioRxiv DO - 10.1101/045260 SP - 045260 AU - Alvaro N. Barbeira AU - Scott P. Dickinson AU - Jason M. Torres AU - Eric S. Torstenson AU - Jiamao Zheng AU - Heather E. Wheeler AU - Kaanan P. Shah AU - Todd Edwards AU - GTEx Consortium AU - Dan L. Nicolae AU - Nancy J. Cox AU - Hae Kyung Im Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/27/045260.abstract N2 - To understand the biological mechanisms underlying thousands of genetic variants robustly associated with complex traits, scalable methods that integrate GWAS and functional data generated by large-scale efforts are needed. Here we propose a method termed MetaXcan that addresses this need by inferring the downstream consequences of genetically regulated components of molecular traits on complex phenotypes using summary data only. MetaXcan allows multiple causal variants and flexible multivariate models enabling the testing of a variety of complex processes under different contexts. As an example application, we trained prediction models of gene expression levels in 44 human tissues and inferred the consequences of their regulation in 40 complex phenotypes. Our examination of this broad set of human tissues revealed many novel genes and re-identified known ones with patterns of regulation in expected as well as unexpected tissues. ER -