Genome-wide Association Study for Alcohol-related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1.

Innes, Hamish; Buch, Stephan; Hutchinson, Sharon; Guha, Indra Neil; Morling, Joanne R.; Barnes, Elleanor; Irving, Will; Forrest, Ewan; Pedergnan, Vincent; Goldberg, David; Aspinall, Esther; Barclay, Stephan; Hayes, Peter; Dillon, John; Nischalke, Hans Dieter; Lutz, Philipp; Spengler, Ulrich; Fischer, Janett; Berg, Thomas; Brosch, Mario; Eyer, Florian; Datz, Christian; Mueller, Sebastian; Peccerella, Teresa; Deltenre, Pierre; Marot, Astrid; Soyka, Michael; McQuillin, Andrew; Morgan, Marsha Y.; Hampe, Jochen; Stickel, Felix

Abstract

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved. BACKGROUND & AIMS: Little is known about genetic factors that affect development of alcohol-related cirrhosis. We performed a genome-wide association study (GWAS) of samples from the United Kingdom Biobank (UKB) to identify polymorphisms associated with risk of alcohol-related liver disease. METHODS: We performed a GWAS of 35,839 participants in the UKB with high intake of alcohol against markers of hepatic fibrosis (FIB-4, APRI and Forns index scores) and hepatocellular injury (levels of aminotransferases). Loci identified in the discovery analysis were tested for their association with alcohol-related cirrhosis in 3 separate European cohorts (phase 1 validation cohort; n=2545). Variants associated with alcohol-related cirrhosis in the validation at a false-discovery rate of less than 20% were then directly genotyped in 2 additional European validation cohorts (phase 2 validation, n=2068). RESULTS: In the GWAS of the discovery cohort, we identified 50 independent risk loci with genome-wide significance (P

Citation

Innes, H., Buch, S., Hutchinson, S., Guha, I. N., Morling, J. R., Barnes, E., …Stickel, F. (2020). Genome-wide Association Study for Alcohol-related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1. Gastroenterology, 159(4), 1276-1289.e7. https://doi.org/10.1053/j.gastro.2020.06.014

• Journal Article Type: Article
• Acceptance Date: Jun 5, 2020
• Online Publication Date: Jun 16, 2020
• Publication Date: Oct 1, 2020
• Deposit Date: Jun 9, 2020
• Publicly Available Date: Jun 17, 2021
• Journal: Gastroenterology
• Print ISSN: 2308-2097
• Electronic ISSN: 1528-0012
• Publisher: Publishing House Zaslavsky
• Peer Reviewed: Peer Reviewed
• Volume: 159
• Issue: 4
• Pages: 1276-1289.e7
• DOI: https://doi.org/10.1053/j.gastro.2020.06.014
• Keywords: Gastroenterology
• Public URL: https://nottingham-repository.worktribe.com/output/4611749
• Publisher URL: https://www.gastrojournal.org/article/S0016-5085(20)34767-3/pdf?referrer=https%3A%2F%2Fdx.doi.org%2F