@article{2ea2153eafc143e0a42d58acb96cba83,
title = "Multitrait genome-wide analyses identify new susceptibility loci and candidate drugs to primary sclerosing cholangitis",
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.",
author = "{The International PSC Study Group} and Younghun Han and Jinyoung Byun and Catherine Zhu and Ryan Sun and Roh, {Julia Y.} and Cordell, {Heather J.} and Lee, {Hyun Sung} and Shaw, {Vikram R.} and Kang, {Sung Wook} and Javad Razjouyan and Cooley, {Matthew A.} and Hassan, {Manal M.} and Siminovitch, {Katherine A.} and Trine Folseraas and David Ellinghaus and Annika Bergquist and Rushbrook, {Simon M.} and Andre Franke and Karlsen, {Tom H.} and Lazaridis, {Konstantinos N.} and Christoph Schramm and David Shapiro and Elizabeth Goode and McGlynn, {Katherine A.} and Roberts, {Lewis R.} and Amos, {Christopher I.}",
note = "Funding Information: We thank all individuals who have contributed their samples and clinical data for the PSC study, and we also thank the international PSC study group for sharing GWAS summary statistics of PSC. We want to acknowledge the participants and investigators of the FinnGen study. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 10/25/2021. Our study was supported by NIH/NCI under award P50 CA210964, by the Cholangiocarcinoma Foundation, and by PSC Partners Seeking a Cure to L.R.R.. C.I.A. is a Research Scholar of the Cancer Prevention Research Interest of Texas (CPRIT) award RR170048. J.Ra. was partially supported by NHLBI under award K25 HL152006 and by Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) award OD032581-01S1. Funding Information: We thank all individuals who have contributed their samples and clinical data for the PSC study, and we also thank the international PSC study group for sharing GWAS summary statistics of PSC. We want to acknowledge the participants and investigators of the FinnGen study. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 10/25/2021. Our study was supported by NIH/NCI under award P50 CA210964, by the Cholangiocarcinoma Foundation, and by PSC Partners Seeking a Cure to L.R.R. C.I.A. is a Research Scholar of the Cancer Prevention Research Interest of Texas (CPRIT) award RR170048. J.Ra. was partially supported by NHLBI under award K25 HL152006 and by Artificial Intelligence/Machine Learning Consortium to Advance Health Equity and Researcher Diversity (AIM-AHEAD) award OD032581-01S1. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-36678-8",
language = "English (US)",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}