Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC. The genetic basis of primary sclerosing cholangitis has only been partially uncovered. Here, the authors perform a multitrait genome-wide association study to provide insight into the genetic etiology of primary sclerosing cholangitis risk and possible therapeutic drug targets.

Automated summary

This study used multitrait joint analyses to explore the genetic contribution and correlations between various clinical and epidemiological traits associated with PSC. Several new risk loci and potential susceptibility genes such as MANBA and IRF5 were identified, and in silico drug screening provided candidate agents for further investigation of pharmacological effects in PSC.