Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.
Nat Commun
; 9(1): 5101, 2018 11 30.
Article
em En
| MEDLINE
| ID: mdl-30504769
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 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálculos Biliares
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article