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.
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| http://dx.doi.org/10.1038/s41467-023-36678-8 | DOI Listing |
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Article Synopsis
- Primary sclerosing cholangitis is a chronic liver condition associated with inflammation and fibrosis of bile ducts, often linked to inflammatory bowel disease and increases the risk of cancer.
- Current treatments mainly offer supportive care, as there are no effective medical therapies available and liver transplantation can prolong life but does not cure the disease.
- Research is ongoing into new therapies aimed at slowing disease progression and alleviating symptoms, with improved trial designs focused on selecting appropriate patients and using better outcome measures to assess treatment effectiveness.
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