LPM: a latent probit model to characterize the relationship among complex traits using summary statistics from multiple GWASs and functional annotations

Abstract

Much effort has been made toward understanding the genetic architecture of complex traits and diseases. Recent results from genome-wide association studies (GWASs) suggest the importance of regulatory genetic effects and pervasive pleiotropy among complex traits. In this study, we propose a unified statistical approach, aiming to characterize relationship among complex traits, and prioritize risk variants by leveraging regulatory information collected in functional annotations. Specifically, we consider a latent probit model (LPM) to integrate summary-level GWAS data and functional annotations. The developed computational framework not only makes LPM scalable to hundreds of annotations and phenotypes, but also ensures its statistically guaranteed accuracy. Through comprehensive simulation studies, we evaluated LPMs performance and compared it with related methods. Then we applied it to analyze 44 GWASs with nine genic category annotations and 127 cell-type specific functional annotations. The results demonstrate the benefits of LPM and gain insights of genetic architecture of complex traits. The LPM package is available at https://github.com/mingjingsi/LPM.