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- Title
Association of sex hormones with non‐alcoholic fatty liver disease: An observational and Mendelian randomization study.
- Authors
Weng, Chenghao; Shao, Zilun; Xiao, Meng; Song, Mingyu; Zhao, Yuxuan; Li, Aolin; Pang, Yuanjie; Huang, Tao; Yu, Canqing; Lv, Jun; Li, Liming; Sun, Dianjianyi
- Abstract
Background and Aims: Sex‐specific associations of sex hormone‐binding globulin (SHBG) and bioavailable testosterone (BAT) with NAFLD remain indeterminate. We aimed to explore observational and genetically determined relationships between each hormone and NAFLD. Methods: We included 187 395 men and 170 193 women from the UK Biobank. Linear and nonlinear Cox regression models and Mendelian randomization (MR) analysis were used to test the associations. Results: During 12.49 years of follow‐up, 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 "U" shape, pnon‐linear <.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 "L‐shaped" MR association between SHBG levels and NAFLD risk was found (pnon‐linear =.016). The bidirectional MR analysis further revealed the effect of NAFLD on SHBG and BAT levels in both sexes. Conclusions: 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.
- Subjects
UNITED Kingdom; NON-alcoholic fatty liver disease; SEX hormones; NONLINEAR regression
- Publication
Liver International, 2024, Vol 44, Issue 5, p1154
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.15866