Title: | Genome-wide association meta-analysis yields 20 loci associated with gallstone disease |
Author: |
... 22 more authors Show all authors |
Date: | 2018-11-30 |
Language: | English |
Scope: | 5101 |
University/Institute: | Háskóli Íslands (HÍ) University of Iceland (UI) |
School: | Heilbrigðisvísindasvið (HÍ) School of Health Sciences (UI) School of Engineering and Natural Sciences (UI) Verkfræði- og náttúruvísindasvið (HÍ) |
Department: | Faculty of Medicine (UI) Læknadeild (HÍ) |
Series: | Nature Communications;9(1) |
ISSN: | 2041-1723 |
DOI: | 10.1038/s41467-018-07460-y |
Subject: | Cholelithiasis; Gall bladder; Genome-wide association studies; Medical genetics; Gallsteinar; Gallblaðra; Erfðafræði; Rannsóknir; læknisfr |
URI: | https://hdl.handle.net/20.500.11815/1384 |
Citation:Ferkingstad, Egil, Oddsson, Asmundur, Gretarsdottir, Solveig, Benonisdottir, Stefania, Thorleifsson, Gudmar, Deaton, Aimee M, . . . Stefansson, Kari. (2018). Genome-wide Association Meta-analysis Yields 20 Loci Associated with Gallstone Disease., Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. 2018, 9(1):5101 Nat Commun.
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Abstract:Gallstones are responsible for one of the most common diseases in the Western world and
are commonly treated with cholecystectomy. We perform a meta-analysis of two genomewide association studies of gallstone disease in Iceland and the UK, totaling 27,174 cases and
736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct
low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid
transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR =
1.36 [1.25–1.49], P = 2.1 × 10–12, MAF = 1%; Val98Ile: OR = 1.15 [1.10–1.20], P = 1.8 × 10–10,
MAF = 4%). We demonstrate that lower bile acid transport by ASBT is accompanied by
greater risk of gallstone disease and highlight the role of the intestinal compartment of the
enterohepatic circulation of bile acids in gallstone disease susceptibility. Additionally, two low
frequency missense variants in SERPINA1 and HNF4A and 17 common variants represent
novel associations with gallstone disease.
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Description:Publisher's version (útgefin grein)
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