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dc.contributor.authorJoshi, Amit
dc.contributor.authorAndersson, Charlotte
dc.contributor.authorBuch, Stephan
dc.contributor.authorStender, Stefan
dc.contributor.authorNoordam, Raymond
dc.contributor.authorWeng, Lu-Chen
dc.contributor.authorWeeke, Peter
dc.contributor.authorAuer, Paul
dc.contributor.authorBoehm, Bernhard
dc.contributor.authorChen, Constance
dc.contributor.authorChoi, Hyon
dc.contributor.authorCurhan, Gary
dc.contributor.authorDenny, Joshua
dc.contributor.authorDe Vivo, Immaculata
dc.contributor.authorEicher, John
dc.contributor.authorEllinghaus, David
dc.contributor.authorFolsom, Aaron
dc.contributor.authorFuchs, Charles
dc.contributor.authorGala, Manish
dc.contributor.authorHaessler, Jeffrey
dc.contributor.authorHofman, Albert
dc.contributor.authorHu, Frank
dc.contributor.authorHunter, David
dc.contributor.authorJanssen, Harry L. A.
dc.contributor.authorKang, Jae
dc.contributor.authorKooperberg, Charles
dc.contributor.authorKraft, Peter
dc.contributor.authorKratzer, Wolfgang
dc.contributor.authorLieb, Wolfgang
dc.contributor.authorLutsey, Pamela
dc.contributor.authorMurad, Sarwa Darwish
dc.contributor.authorNordestgaard, Børge G.
dc.contributor.authorPasquale, Louis
dc.contributor.authorReiner, Alex
dc.contributor.authorRidker, Paul
dc.contributor.authorRimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600
dc.contributor.authorRose, Lynda
dc.contributor.authorShaffer, Christian
dc.contributor.authorSchafmayer, Clemens
dc.contributor.authorTamimi, Rulla
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorVölker, Uwe
dc.contributor.authorVölzke, Henry
dc.contributor.authorWakabayashi, Yoshiyuki
dc.contributor.authorWiggs, Janey
dc.contributor.authorZhu, Jun
dc.contributor.authorRoden, Dan
dc.contributor.authorStricker, Bruno
dc.contributor.authorTang, Weihong
dc.contributor.authorTeumer, Alexander
dc.contributor.authorHampe, Jochen
dc.contributor.authorTybjærg-Hansen, Anne
dc.contributor.authorChasman, Daniel
dc.contributor.authorChan, Andrew
dc.contributor.authorJohnson, Andrew
dc.date.accessioned2019-08-27T18:05:52Z
dc.date.issued2016
dc.identifier.citationJoshi, Amit D., Charlotte Andersson, Stephan Buch, Stefan Stender, Raymond Noordam, Lu-Chen Weng, Peter E. Weeke, et al. 2016. “Four Susceptibility Loci for Gallstone Disease Identified in a Meta-Analysis of Genome-Wide Association Studies.” Gastroenterology 151 (2): 351–363.e28. https://doi.org/10.1053/j.gastro.2016.04.007.
dc.identifier.issn0016-5085
dc.identifier.issn1528-0012
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41263070*
dc.description.abstractBACKGROUND and 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 = 2.44 x 10(-60)) and rs4245791 (OR, 1.27; P = 1.90 x 10(-34)). We also identified and/or replicated associations for rs9843304 in TM4SF4 (OR, 1.12; 95% CI, 1.08-1.16; P = 6.09 x 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 = 2.24 x 10-11, rs1260326 in glucokinase regulatory protein (OR, 1.12; 95% CI, 1.07-1.17; P = 2.55 x 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 = 8.84 x 10(-9)). Among individuals of African American and Hispanic American ancestry, rs11887534 and rs4245791 were associated positively with gallstone disease risk, whereas the 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.
dc.language.isoen_US
dc.publisherElsevier
dash.licenseOAP
dc.titleFour Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-wide Association Studies
dc.typeJournal Article
dc.description.versionAccepted Manuscript
dc.relation.journalGastroenterology
dash.depositing.authorRimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600
dc.date.available2019-08-27T18:05:52Z
dash.workflow.comments1Science Serial ID 34560
dc.identifier.doi10.1053/j.gastro.2016.04.007
dash.source.volume151;2
dash.source.page351


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