{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:42:15Z","timestamp":1784634135538,"version":"3.55.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,8]]},"abstract":"\n Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts. We extracted genetic associations with gallstone disease from the Global Biobank Engine (GBE), an online browser of genome\u2010wide associations in UK Biobank participants (14,940 cases and 322,268 controls). Significant associations (\n P<\/jats:italic>\n < 5 \u00d7 10\n \u20138<\/jats:sup>\n ) were retested in two Copenhagen cohorts (comprising 1,522 cases and 18,266 controls). In the Copenhagen cohorts, we also tested whether a genetic risk score was associated with gallstone disease and whether individual gallstone loci were associated with plasma levels of lipids, lipoproteins, and liver enzymes. We identified 19 loci to be associated with gallstone disease in the GBE. Of these, 12 were replicated in the Copenhagen cohorts, including six previously unknown loci (in hepatocyte nuclear factor 4 alpha [\n HNF4A<\/jats:italic>\n ], fucosyltransferase 2, serpin family A member 1 [\n SERPINA1<\/jats:italic>\n ], jumonji domain containing 1C,\n AC074212.3<\/jats:italic>\n , and solute carrier family 10A member 2 [\n SLC10A2<\/jats:italic>\n ]) and six known loci (in adenosine triphosphate binding cassette subfamily G member 8 [\n ABCG8<\/jats:italic>\n ], sulfotransferase family 2A member 1, cytochrome P450 7A1, transmembrane 4 L six family member 4,\n ABCB4<\/jats:italic>\n , and tetratricopeptide repeat domain 39B). Five of the gallstone associations are protein\u2010altering variants, and three (\n HNF4A<\/jats:italic>\n p.Thr139Ile,\n SERPINA1<\/jats:italic>\n p.Glu366Lys, and\n SLC10A2<\/jats:italic>\n p.Pro290Ser) conferred per\u2010allele odds ratios for gallstone disease of 1.30\u20101.36. Individuals with a genetic risk score >2.5 (prevalence 1%) had a 5\u2010fold increased risk of gallstones compared to those with a score <1.0 (11%). Of the 19 lithogenic loci, 11 and ten exhibited distinct patterns of association with plasma levels of lipids and liver enzymes, respectively.\n Conclusion<\/jats:italic>\n : We identified six susceptibility loci for gallstone disease.\n <\/jats:p>","DOI":"10.1002\/hep.30313","type":"journal-article","created":{"date-parts":[[2018,10,16]],"date-time":"2018-10-16T08:57:41Z","timestamp":1539680261000},"page":"597-609","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":26,"title":["Identification and Replication of Six Loci Associated With Gallstone Disease"],"prefix":"10.1097","volume":"70","author":[{"given":"Helene","family":"Gellert\u2010Kristensen","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry,Rigshospitalet,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawar","family":"Dalila","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry,Rigshospitalet,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sune","family":"Fallgaard Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, The Copenhagen General Population Study,Herlev and Gentofte Hospital,Copenhagen,Denmark"},{"name":"The Copenhagen General Population Study,Herlev and Gentofte Hospital,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00f8rge","family":"Gr\u00f8nne Nordestgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, The Copenhagen General Population Study,Herlev and Gentofte Hospital,Copenhagen,Denmark"},{"name":"The Copenhagen General Population Study,Herlev and Gentofte Hospital,Copenhagen,Denmark"},{"name":"The Copenhagen City Heart Study,Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Tybj\u00e6rg\u2010Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry,Rigshospitalet,Copenhagen,Denmark"},{"name":"The Copenhagen General Population Study,Herlev and Gentofte Hospital,Copenhagen,Denmark"},{"name":"The Copenhagen City Heart Study,Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospitals and Faculty of Health and Medical Sciences, University of Copenhagen,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-5900","authenticated-orcid":false,"given":"Stefan","family":"Stender","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry,Rigshospitalet,Copenhagen,Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"hep30313-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"16024","DOI":"10.1038\/nrdp.2016.24","article-title":"Gallstones","volume":"2","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"hep30313-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0140-6736(06)69044-2","article-title":"Cholesterol gallstone disease","volume":"368","year":"2006","journal-title":"Lancet"},{"key":"hep30313-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1053\/j.gastro.2008.12.015","article-title":"Burden of digestive diseases in the United States part I: overall and upper gastrointestinal 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