RT Journal Article
SR Electronic
T1 Integrating tissue specific mechanisms into GWAS summary results
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 045260
DO 10.1101/045260
A1 Alvaro Barbeira
A1 Scott P. Dickinson
A1 Jason M. Torres
A1 Eric S. Torstenson
A1 Jiamao Zheng
A1 Heather E. Wheeler
A1 Kaanan P. Shah
A1 Todd Edwards
A1 GTEx Consortium
A1 Dan L. Nicolae
A1 Nancy J. Cox
A1 Hae Kyung Im
YR 2016
UL http://biorxiv.org/content/early/2016/10/11/045260.abstract
AB 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.