RT Journal Article SR Electronic T1 Modeling prediction error improves power of transcriptome-wide association studies JF bioRxiv FD Cold Spring Harbor Laboratory SP 108316 DO 10.1101/108316 A1 Kunal Bhutani A1 Abhishek Sarkar A1 Yongjin Park A1 Manolis Kellis A1 Nicholas J. Schork YR 2017 UL http://biorxiv.org/content/early/2017/02/14/108316.abstract AB Transcriptome-wide association studies (TWAS) test for associations between imputed gene expression levels and phenotypes in GWAS cohorts using models of transcriptional regulation learned from reference transcriptomes. However, current methods for TWAS only use point estimates of imputed expression and ignore uncertainty in the prediction. We develop a novel two-stage Bayesian regression method which incorporates uncertainty in imputed gene expression and achieves higher power to detect TWAS genes than existing TWAS methods as well as standard methods based on missing value and measurement error theory. We apply our method to GTEx whole blood transcriptomes and GWAS cohorts for seven diseases from the Wellcome Trust Case Control Consortium and find 45 TWAS genes, of which 17 do not overlap previously reported case-control GWAS or differential expression associations. Surprisingly, we replicate only 2 of 40 previously reported TWAS genes after accounting for uncertainty in the prediction.