Opin vísindi

Genome-wide association meta-analysis yields 20 loci associated with gallstone disease

Genome-wide association meta-analysis yields 20 loci associated with gallstone disease

Title: Genome-wide association meta-analysis yields 20 loci associated with gallstone disease
Author: Ferkingstad, Egil   orcid.org/0000-0001-8090-7988
Oddsson, Asmundur   orcid.org/0000-0002-4606-5163
Gretarsdottir, Solveig
Benonisdottir, Stefania   orcid.org/0000-0001-5019-514X
Thorleifsson, Gudmar   orcid.org/0000-0003-4623-9087
Deaton, Aimee M.
Jónsson, Stefán
Stefánsson, Ólafur A.
Norðdahl, Guðmundur L.
Zink, Florian
... 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

Show full item record


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.


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.


Publisher's version (útgefin grein)


Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

Files in this item

This item appears in the following Collection(s)