{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:36:42Z","timestamp":1792805802192,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>The risk factors of cholelithiasis have not been clearly identified, especially for total cholesterol. Here, we try to identify these causal risk factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We obtained genetic variants associated with the exposures at the genome\u2010wide significance (<jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0&lt;\u00a05\u00a0\u00d7\u00a010<jats:sup>\u22128<\/jats:sup>) level from corresponding genome\u2010wide association studies. Summary\u2010level statistical data for cholelithiasis were obtained from FinnGen and UK Biobank (UKB) consortia. Both univariable and multivariable Mendelian randomization (MR) analyses were conducted to identify causal risk factors of cholelithiasis. Results from FinnGen and UKB were combined using the fixed\u2010effect model. In FinnGen, the odds of cholelithiasis increased per 1\u2010SD increase of body mass index (BMI) (OR\u00a0=\u00a01.631, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a02.16\u00a0\u00d7\u00a010<jats:sup>\u22127<\/jats:sup>), together with body fat percentage (OR\u00a0=\u00a02.108, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a04.56\u00a0\u00d7\u00a010<jats:sup>\u22123<\/jats:sup>) and fasting insulin (OR\u00a0=\u00a02.340, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a09.09\u00a0\u00d7\u00a010<jats:sup>\u22123<\/jats:sup>). The odds of cholelithiasis would also increase with lowering of total cholesterol (OR\u00a0=\u00a00.789, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a08.34\u00a0\u00d7\u00a010<jats:sup>\u22125<\/jats:sup>) and low\u2010density lipoprotein\u2013cholesterol (LDL\u2010C) (OR\u00a0=\u00a00.792, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a02.45\u00a0\u00d7\u00a010<jats:sup>\u22124<\/jats:sup>). However, LDL\u2010C was not significant in multivariable MR. In UKB, the results of BMI, body fat percentage, total cholesterol, and LDL\u2010C were replicated. In meta\u2010analysis, the liability to type 2 diabetes mellitus and smoking could also increase the risk of cholelithiasis. Moreover, there were no associations with other predominant risk factors.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our MR study corroborated the risk factors of cholelithiasis from previous MR studies. Furthermore, lower total cholesterol level could be an independent risk factor.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32183","type":"journal-article","created":{"date-parts":[[2021,10,9]],"date-time":"2021-10-09T06:09:12Z","timestamp":1633759752000},"page":"785-796","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":260,"title":["Insights into modifiable risk factors of cholelithiasis: A\u00a0Mendelian randomization study"],"prefix":"10.1097","volume":"75","author":[{"given":"Lanlan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery,The First Hospital of Jilin University,Changchun,Jilin,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery,The First Hospital of Jilin University,Changchun,Jilin,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics,The China\u2010Japan Union Hospital of Jilin University,Changchun,Jilin,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology,College of Basic Medical Sciences,Jilin University,Changchun,Jilin,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology,Huashan Hospital,Shanghai Medical College,Fudan University,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4656-4955","authenticated-orcid":false,"given":"Guoyue","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery,The First Hospital of Jilin University,Changchun,Jilin,China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"hep32183-bib-0001-20250824","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":"hep32183-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"172","DOI":"10.5009\/gnl.2012.6.2.172","article-title":"Epidemiology of gallbladder disease: cholelithiasis and cancer","volume":"6","year":"2012","journal-title":"Gut Liv"},{"key":"hep32183-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1002\/hep.26563","article-title":"Elevated body mass index as a causal risk factor for symptomatic gallstone disease: a Mendelian randomization study","volume":"58","year":"2013","journal-title":"Hepatology"},{"key":"hep32183-bib-0004-20250824","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/17474124.2019.1549988","article-title":"Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention","volume":"13","year":"2019","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"hep32183-bib-0005-20250824","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/hep.510310206","article-title":"Association of diabetes, serum insulin, and C\u2010peptide with gallbladder disease","volume":"31","year":"2000","journal-title":"Hepatology"},{"key":"hep32183-bib-0006-20250824","article-title":"Obesity, type 2 diabetes, lifestyle factors, and risk of gallstone disease: a Mendelian randomization investigation","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"hep32183-bib-0007-20250824","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MOG.0000000000000416","article-title":"Nonalcoholic fatty liver disease, cholesterol gallstones, and cholecystectomy: new insights on a complex relationship","volume":"34","year":"2018","journal-title":"Curr Opin Gastroenterol"},{"key":"hep32183-bib-0008-20250824","first-page":"187","article-title":"The effects of serum cholesterol, LDL, and HDL levels on gallstone cholesterol concentration","volume":"29","year":"2013","journal-title":"Pak J Med Sci"},{"key":"hep32183-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1002\/hep.510260401","article-title":"Factors associated with gallstone disease in the MICOL experience. 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