Much effort has been made toward understanding the genetic architecture of complex traits and diseases. In the past decade, fruitful GWAS findings have highlighted the important role of regulatory variants and pervasive pleiotropy. Because of the accumulation of GWAS data on a wide range of phenotypes and high-quality functional annotations in different cell types, it is timely to develop a statistical framework to explore the genetic architecture of human complex traits by integrating rich data resources.


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 LPM’s performance and compared it with related methods. Then, we applied it to analyze 44 GWASs with 9 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.

Availability and implementation

The LPM package, all simulation codes and real datasets in this study are available at

Supplementary information

Supplementary data are available at Bioinformatics online.

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