{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:43:47Z","timestamp":1789231427171,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103920"],"award-info":[{"award-number":["82103920"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFC2003405"],"award-info":[{"award-number":["2020YFC2003405"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Sex\u2010specific associations of sex hormone\u2010binding globulin (SHBG) and bioavailable testosterone (BAT) with NAFLD remain indeterminate. We aimed to explore observational and genetically determined relationships between each hormone and NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 187\u2009395 men and 170\u2009193 women from the UK Biobank. Linear and nonlinear Cox regression models and Mendelian randomization (MR) analysis were used to test the associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During 12.49\u2009years of follow\u2010up, 2209 male and 1886 female NAFLD cases were documented. Elevated SHBG levels were linearly associated with a lower risk of NAFLD in women (HR (95% CI), .71 (.63, .79)), but not in men (a \u201cU\u201d shape, <jats:italic>p<\/jats:italic><jats:sub>non\u2010linear<\/jats:sub>\u2009&lt;\u2009.001). Higher BAT levels were associated with a lower NAFLD risk in men (HR (95% CI), .81 (.71, .93)) but a higher risk in women (HR (95% CI): 1.25 (1.15, 1.36)). Genetically determined SHBG and BAT levels were linearly associated with NAFLD risk in women (OR (95% CI): .57 (.38, .87) and 2.21 (1.41, 3.26) respectively); in men, an \u201cL\u2010shaped\u201d MR association between SHBG levels and NAFLD risk was found (<jats:italic>p<\/jats:italic><jats:sub>non\u2010linear<\/jats:sub>\u2009=\u2009.016). The bidirectional MR analysis further revealed the effect of NAFLD on SHBG and BAT levels in both sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Consistently, linear associations of lower SHBG and higher BAT levels with increased NAFLD risk were both conventionally and genetically found in women, while in men, SHBG acts in a nonlinear manner. In addition, NAFLD may affect SHBG and BAT levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15866","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T12:09:43Z","timestamp":1707739783000},"page":"1154-1166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association of sex hormones with non\u2010alcoholic fatty liver disease: An observational and Mendelian randomization study"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5463-4393","authenticated-orcid":false,"given":"Chenghao","family":"Weng","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Peking University Health Science Center  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilun","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health Peking 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