@article {836891,
	title = {Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies.},
	journal = {Gastroenterology},
	volume = {151},
	number = {2},
	year = {2016},
	month = {2016 Aug},
	pages = {351-363.e28},
	abstract = {BACKGROUND \&amp; AIMS: A genome-wide association study (GWAS) of 280 cases identified the hepatic cholesterol transporter ABCG8 as a locus associated with risk for gallstone disease, but findings have not been reported from any other GWAS of this phenotype. We performed a large-scale, meta-analysis of GWASs of individuals of European ancestry with available prior genotype data, to identify additional genetic risk factors for gallstone disease. METHODS: We obtained per-allele odds ratio (OR) and standard error estimates using age- and sex-adjusted logistic regression models within each of the 10 discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62,797 controls. RESULTS: We observed independent associations for 2 single-nucleotide polymorphisms at the ABCG8 locus: rs11887534 (OR, 1.69; 95\% confidence interval [CI], 1.54-1.86; P\&nbsp;= 2.44\&nbsp;{\texttimes} 10(-60)) and rs4245791 (OR, 1.27; P\&nbsp;= 1.90\&nbsp;{\texttimes} 10(-34)). We also identified and/or replicated associations for rs9843304 in TM4SF4 (OR, 1.12; 95\% CI, 1.08-1.16; P\&nbsp;= 6.09\&nbsp;{\texttimes} 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95\% CI, 1.12-1.21; P\&nbsp;= 2.24\&nbsp;{\texttimes} 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95\% CI, 1.07-1.17; P\&nbsp;=\&nbsp;2.55\&nbsp;{\texttimes} 10(-10)), and rs6471717 near CYP7A1 (encodes an enzyme that catalyzes conversion of cholesterol to primary bile acids) (OR, 1.11; 95\% CI, 1.08-1.15; P\&nbsp;= 8.84\&nbsp;{\texttimes} 10(-9)). Among individuals of African American and Hispanic American ancestry, rs11887534 and rs4245791 were associated positively with gallstone disease risk, whereas the\&nbsp;association for the rs1260326 variant was inverse. CONCLUSIONS: In this large-scale GWAS of gallstone disease, we identified 4 loci in genes that have putative functions in cholesterol metabolism and transport, and sulfonylation of bile acids or hydroxysteroids.},
	issn = {1528-0012},
	doi = {10.1053/j.gastro.2016.04.007},
	author = {Joshi, Amit D and Andersson, Charlotte and Buch, Stephan and Stender, Stefan and Noordam, Raymond and Weng, Lu-Chen and Weeke, Peter E and Auer, Paul L and Boehm, Bernhard and Chen, Constance and Choi, Hyon and Curhan, Gary and Denny, Joshua C and De Vivo, Immaculata and Eicher, John D and Ellinghaus, David and Folsom, Aaron R and Fuchs, Charles and Gala, Manish and Haessler, Jeffrey and Hofman, Albert and Hu, Frank and Hunter, David J and Janssen, Harry L A and Kang, Jae H and Kooperberg, Charles and Kraft, Peter and Kratzer, Wolfgang and Lieb, Wolfgang and Lutsey, Pamela L and Darwish Murad, Sarwa and Nordestgaard, B{\o}rge G and Pasquale, Louis R and Reiner, Alex P and Ridker, Paul M and Rimm, Eric and Rose, Lynda M and Shaffer, Christian M and Schafmayer, Clemens and Tamimi, Rulla M and Uitterlinden, Andr{\'e} G and V{\"o}lker, Uwe and V{\"o}lzke, Henry and Wakabayashi, Yoshiyuki and Wiggs, Janey L and Zhu, Jun and Roden, Dan M and Stricker, Bruno H and Tang, Weihong and Teumer, Alexander and Hampe, Jochen and Tybj{\ae}rg-Hansen, Anne and Chasman, Daniel I and Chan, Andrew T and Johnson, Andrew D}
}
