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ToolsThe International PSC Study Group (2023) Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis. Nature Communications, 14 (1). ISSN 2041-1723
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Abstract
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.
| Item Type: | Article |
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| Additional Information: | Data availability: The summary statistics of PSC from MTAG are publicly available at https://github.com/biomedicaldatascience/PSC_MTAG. The GWAS summary-level data analyzed in this study are available in the NHGRI-EBI GWAS Catalog [https://www.ebi.ac.uk/gwas/] and the MRC IEU OpenGWAS database [https://gwas.mrcieu.ac.uk/] for previously published GWAS summary statistics, Neale’s lab repository for UK Biobank GWAS summary statistics [https://github.com/Nealelab/UK_Biobank_GWAS], and FinnGen repository for Finnish Biobank GWAS summary statistics r6 [https://finngen.gitbook.io/documentation/v/r6/data-download]. The accessible links and reference information for the GWAS summary-level data (mapped to Genome Assembly GRCh37) used in this study can be found in Supplementary Data 1 and 2. Non-commercial DrugBank datasets (v5.1.9) are available and access can be obtained by the academic license [https://go.drugbank.com/releases/latest]. The data including all variant-gene cis-eQTL associations tested in each tissue (GTEx v8) are available in a requester pays bucket on Google Cloud Platform (GCP) [https://gtexportal.org/home/datasets; https://console.cloud.google.com/storage/browser/gtex-resources]. The immune-related genes can be obtained in the InnateDB portal [https://www.innatedb.com/redirect.do?go=resourcesGeneLists]. |
| Uncontrolled Keywords: | general chemistry,general biochemistry,genetics and molecular biology,general,general physics and astronomy ,/dk/atira/pure/subjectarea/asjc/1600/1600 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 05 Aug 2026 08:10 |
| Last Modified: | 11 Aug 2026 15:45 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/103997 |
| DOI: | 10.1038/s41467-023-36678-8 |
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