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

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 genome-wide 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 o

SUBMITTER: Ferkingstad E 

PROVIDER: S-EPMC6269469 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature