{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:16:46Z","timestamp":1792819006810,"version":"4.5.0"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>Early identification of modifiable risk factors is essential for the prevention of nonalcoholic fatty liver disease (NAFLD). We aimed to systematically explore the relationships between genetically predicted modifiable risk factors and NAFLD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>We applied univariable and multivariable Mendelian randomization analyses to explore the relationships between 35 modifiable risk factors and NAFLD. We also evaluated the combined results in three independent large genome\u2010wide association studies. Genetically predicted alcohol frequency, elevated serum levels of liver enzymes, triglycerides, C\u2010reactive protein, and obesity traits, including body mass index, waist circumference, and body fat mass, were associated with increased risks of NAFLD (all with <jats:italic toggle=\"yes\">p<\/jats:italic>\u2009&lt;\u20090.05). Poor physical condition had a suggestive increased risk for NAFLD (odds ratio [OR]\u00a0=\u00a02.63, <jats:italic toggle=\"yes\">p<\/jats:italic>\u00a0=\u00a00.042). Genetically instrumented type 2 diabetes (T2DM), hypothyroidism, and hypertension all increased the risk for NAFLD, and the ORs (95% confidence interval) were 1.508 (1.20\u20131.90), 13.08 (1.53\u2013111.65), and 3.11 (1.33\u20137.31) for a 1\u2010U increase in log\u2010transformed odds, respectively. The positive associations of T2DM and hypertension with NAFLD remained significant in multivariable analyses. The combined results from the discovery and two replication datasets further confirmed that alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension significantly increase the risk of NAFLD, whereas higher education and high\u2010density lipoprotein cholesterol (HDL\u2010cholesterol) could lower NAFLD risk.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Genetically predicted alcohol frequency, elevated serum liver enzymes, poor physical condition, obesity traits, T2DM, and hypertension were associated with an increased risk of NAFLD, whereas higher education and HDL\u2010cholesterol were associated with a decreased risk of NAFLD.<\/jats:p>\n          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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hangkai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhening","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Zhejiang Provincial Clinical Research Center for Digestive Diseases, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4842-3646","authenticated-orcid":false,"given":"Chaohui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Zhejiang Provincial Clinical Research Center for Digestive Diseases, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6017-3745","authenticated-orcid":false,"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China"},{"name":"Department of Gastroenterology, Ningbo First Hospital, Ningbo, China"},{"name":"Zhejiang Provincial Clinical Research Center for Digestive Diseases, Hangzhou, 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