Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study
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Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study. / Cai, Xinting; Thorand, Barbara; Hohenester, Simon; Prehn, Cornelia; Cecil, Alexander; Adamski, Jerzy; Zeller, Tanja; Dennis, Andrea; Banerjee, Rajarshi; Peters, Annette; Yaghootkar, Hanieh; Nano, Jana.
In: FRONT ENDOCRINOL, Vol. 14, 2023, p. 1223162.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Association of sex hormones and sex hormone-binding globulin with liver fat in men and women: an observational and Mendelian randomization study
AU - Cai, Xinting
AU - Thorand, Barbara
AU - Hohenester, Simon
AU - Prehn, Cornelia
AU - Cecil, Alexander
AU - Adamski, Jerzy
AU - Zeller, Tanja
AU - Dennis, Andrea
AU - Banerjee, Rajarshi
AU - Peters, Annette
AU - Yaghootkar, Hanieh
AU - Nano, Jana
N1 - Copyright © 2023 Cai, Thorand, Hohenester, Prehn, Cecil, Adamski, Zeller, Dennis, Banerjee, Peters, Yaghootkar and Nano.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses.METHODS: The observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies.RESULTS: In the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value <0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (β = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (β = -0.36, 95% CI: -0.61, -0.12).CONCLUSION: Our results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation.
AB - BACKGROUND: Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous sex hormones, including testosterone (T), and SHBG with liver fat using complementary observational and Mendelian randomization (MR) analyses.METHODS: The observational analysis included a total of 2,239 participants (mean age 60 years; 35% postmenopausal women) from the population-based KORA study (average follow-up time: 6.5 years). We conducted linear regression analysis to investigate the sex-specific associations of sex hormones and SHBG with liver fat, estimated by fatty liver index (FLI). For MR analyses, we selected genetic variants associated with sex hormones and SHBG and extracted their associations with magnetic resonance imaging measured liver fat from the largest up to date European genome-wide associations studies.RESULTS: In the observational analysis, T, dihydrotestosterone (DHT), progesterone and 17α-hydroxyprogesterone (17-OHP) were inversely associated with FLI in men, with beta estimates ranging from -4.23 to -2.30 [p-value <0.001 to 0.003]. Whereas in women, a positive association of free T with FLI (β = 4.17, 95%CI: 1.35, 6.98) was observed. SHBG was inversely associated with FLI across sexes [men: -3.45 (-5.13, -1.78); women: -9.23 (-12.19, -6.28)]. No causal association was found between genetically determined sex hormones and liver fat, but higher genetically determined SHBG was associated with lower liver fat in women (β = -0.36, 95% CI: -0.61, -0.12).CONCLUSION: Our results provide suggestive evidence for a causal association between SHBG and liver fat in women, implicating the protective role of SHBG against liver fat accumulation.
KW - Male
KW - Humans
KW - Female
KW - Middle Aged
KW - Sex Hormone-Binding Globulin/genetics
KW - Mendelian Randomization Analysis
KW - Dihydrotestosterone
KW - Fatty Liver/epidemiology
U2 - 10.3389/fendo.2023.1223162
DO - 10.3389/fendo.2023.1223162
M3 - SCORING: Journal article
C2 - 37900132
VL - 14
SP - 1223162
JO - FRONT ENDOCRINOL
JF - FRONT ENDOCRINOL
SN - 1664-2392
ER -
