{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:40:56Z","timestamp":1790750456771,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic syndrome (MetS) has been associated with digestive system diseases, and recent observational studies have suggested an association between MetS and cholelithiasis. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect of MetS on cholelithiasis using Mendelian randomization (MR) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single nucleotide polymorphisms (SNPs) of MetS and its components were extracted from the public genetic variation summary database. The inverse variance weighting method (IVW), weighted median method, and MR-Egger regression were used to evaluate the causal relationship. A sensitivity analysis was performed to ensure the stability of the results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IVW showed that MetS increased the risk of cholelithiasis (OR = 1.28, 95% CI = 1.13\u20131.46, P = 9.70E\u221205), and the weighted median method had the same result (OR = 1.49, 95% CI = 1.22\u20131.83, P = 5.68E\u221205). In exploring the causal relationship between MetS components and cholelithiasis, waist circumference (WC) was significantly associated with cholelithiasis. IVW analysis (OR = 1.48, 95% CI = 1.34\u20131.65, P = 1.15E\u221213), MR-Egger regression (OR = 1.62, 95% CI = 1.15\u20132.28, P = 0.007), and weighted median (OR = 1.73, 95% CI = 1.47\u20132.04, P = 1.62E\u221211) all found the same results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study indicated that MetS increases the incidence of cholelithiasis, especially in MetS patients with abdominal obesity. Control and treatment of MetS can effectively reduce the risk of gallstone formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2023.1180903","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:47:26Z","timestamp":1686271646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":47,"title":["Causal association between metabolic syndrome and cholelithiasis: a Mendelian randomization study"],"prefix":"10.3389","volume":"14","author":[{"given":"Qi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaqin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langyi","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foqiang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.10.1345","article-title":"National surveillance for type 2 diabetes mellitus in Taiwanese children","volume":"290","author":"Wei","year":"2003","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jegh.2017.07.004","article-title":"Assessment of metabolic syndrome in kashmiri population with type 2 diabetes employing the standard criteria's given by WHO, NCEPATP III and IDF","volume":"7","author":"Lone","year":"2017","journal-title":"J Epidemiol Glob Health"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00326","article-title":"The association between metabolic syndrome and gastric cancer in Chinese","volume":"8","author":"Li","year":"2018","journal-title":"Front Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"16024","DOI":"10.1038\/nrdp.2016.24","article-title":"Gallstones","volume":"2","author":"Lammert","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69044-2","article-title":"Cholesterol gallstone disease","volume":"368","author":"Portincasa","year":"2006","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqaa154","article-title":"A healthy lifestyle pattern and the risk of symptomatic gallstone disease: results from 2 prospective cohort studies","volume":"112","author":"Wirth","year":"2020","journal-title":"Am J Clin Nutr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2011.06.018","article-title":"Diabetes and gallstones","volume":"43","author":"Attili.","year":"2011","journal-title":"Dig Liver Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000450","article-title":"Contributory risk and management of comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: a scientific statement from the American heart association","volume":"134","author":"Bozkurt","year":"2016","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"29937","DOI":"10.1038\/srep29937","article-title":"The association between gallstones and metabolic syndrome in urban han Chinese: a longitudinal cohort study","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.jhep.2006.01.026","article-title":"Gallbladder disease is associated with insulin resistance in a high risk Hispanic population","volume":"45","author":"Nervi","year":"2006","journal-title":"J Hepatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i11.1653","article-title":"Metabolic syndrome as a risk factor for gallstone disease","volume":"11","author":"Mendez-Sanchez","year":"2005","journal-title":"World J Gastroenterol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016010098","article-title":"Mendelian randomization as an approach to assess causality using observational data","volume":"27","author":"Sekula","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1093\/ije\/dyh132","article-title":"Mendelian randomization: prospects, potentials, and limitations","volume":"33","author":"Smith","year":"2004","journal-title":"Int J Epidemiol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/ije\/dyg070","article-title":"Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease","volume":"32","author":"Smith","year":"2003","journal-title":"Int J Epidemiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0631-4","article-title":"Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics","volume":"52","author":"Morrison","year":"2020","journal-title":"Nat Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"a041302","DOI":"10.1101\/cshperspect.a041302","article-title":"Mendelian randomization","volume":"12","author":"Birney","year":"2022","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1093\/ije\/dyv071","article-title":"Mendelian randomization studies: a review of the approaches used and the quality of reporting","volume":"44","author":"Boef","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2337\/db22-0478","article-title":"Disentangling genetic risks for metabolic syndrome","volume":"71","author":"van Walree","year":"2022","journal-title":"Diabetes"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyq151","article-title":"Power and instrument strength requirements for mendelian randomization studies using multiple genetic variants","volume":"40","author":"Pierce","year":"2011","journal-title":"Int J Epidemiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2274","article-title":"A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance","volume":"44","author":"Manning","year":"2012","journal-title":"Nat Genet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels","volume":"45","author":"Willer","year":"2013","journal-title":"Nat Genet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"The MR-base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"Elife"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080","article-title":"Burgess. mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22207","article-title":"Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in mendelian randomization studies from a practitioner's perspective","volume":"43","author":"Ong","year":"2019","journal-title":"Genet Epidemiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/s41598-023-28088-z","article-title":"Sex-specific differences in the associations of metabolic syndrome or components with gallstone disease in Chinese euthyroid population","volume":"13","author":"Jiang","year":"2023","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15568","article-title":"Association between metabolic syndrome and incidence of cholelithiasis in the Korean population","volume":"36","author":"Kim","year":"2021","journal-title":"J Gastroenterol Hepatol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.322.7288.716","article-title":"Treatment of obesity: need to focus on high risk abdominally obese patients","volume":"322","author":"Despres","year":"2001","journal-title":"BMJ"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-200609000-00016","article-title":"Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults","volume":"40","author":"Chen","year":"2006","journal-title":"J Clin Gastroenterol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i28.4536","article-title":"A population-based follow-up study on gallstone disease among type 2 diabetics in kinmen, Taiwan","volume":"12","author":"Tung","year":"2006","journal-title":"World J Gastroenterol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2021.06.044","article-title":"Obesity, adiposity, and risk of symptomatic gallstone disease according to genetic susceptibility","volume":"20","author":"Lim","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B33","doi-asserted-by":"publisher","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","author":"Stender","year":"2013","journal-title":"Hepatology"},{"key":"B34","article-title":"Atherosclerosis in relation to cholelithiasis and cholesterolosis","volume":"53","author":"Zahor","year":"1976","journal-title":"Bull World Health Organ"},{"key":"B35","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/1471-2296-15-138","article-title":"The association of metabolic syndrome and its factors with gallstone disease","volume":"15","author":"Lin","year":"2014","journal-title":"BMC Fam Pract"},{"key":"B36","article-title":"Risk factors and pathogenesis of cholesterol gallstones: state of the art","volume":"3","author":"Amigo","year":"1999","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2174\/138161211798220909","article-title":"Lipid lowering drugs and gallstones: a therapeutic option","volume":"17","author":"Lioudaki","year":"2011","journal-title":"Curr Pharm Des"},{"key":"B38","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.gassur.2006.04.005","article-title":"Insulin resistance causes human gallbladder dysmotility","volume":"10","author":"Nakeeb","year":"2006","journal-title":"J Gastrointest Surg"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1180903\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:47:31Z","timestamp":1686271651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1180903\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,9]]},"references-count":38,"alternative-id":["10.3389\/fendo.2023.1180903"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1180903","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,9]]},"article-number":"1180903"}}