scholarly journals Causal effect of sex hormone-binding globulin and testosterone on coronary heart disease: A multivariable and network Mendelian randomization analysis

2021 ◽  
Author(s):  
Yunxia Li ◽  
Shucheng Si ◽  
Lei Hou ◽  
Tonghui Yuan ◽  
Xiaolu Chen ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

Abstract 011: Sex Hormone-Binding Globulin (SHBG) and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Brian H Chen ◽  
Kathleen Brennan ◽  
Atsushi Goto ◽  
Yiqing Song ◽  
Najib Aziz ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Mendelian Randomization ◽  
Diabetes Risk ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Clinical Diabetes ◽  
Hormone Binding ◽  
Mendelian Randomization Analysis ◽  
Asian Pacific ◽  
Randomization Analysis

BACKGROUND: Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) levels and risk of clinical diabetes in Whites. However, it remains unknown whether this relation extends to other racial/ethnic populations. METHODS: We evaluated the association between baseline levels of SHBG and risk of clinical diabetes in the Women’s Health Initiative Observational Study. Over a median follow-up of 5.9 years, 542 postmenopausal women developed clinical diabetes (338 Blacks, 128 Hispanics, 76 Asians) and were matched to 1,110 controls (707 Blacks, 249 Hispanics, 154 Asians). To complement our protein-level findings, we also genotyped 5 SHBG polymorphisms. We performed Mendelian randomization analysis to assess the potential causal relation between SHBG levels and risk of clinical diabetes. RESULTS: Overall, higher levels of SHBG at baseline were associated with a significantly lower risk of clinical diabetes (Relative risk [RR]=0.24, 95% confidence interval [CI]=0.15-0.39 for highest versus lowest quartile of SHBG, adjusted for BMI and other known diabetes risk factors). The associations remained consistent across ethnic groups (p-for-heterogeneity=0.72): RR=0.29 (95%CI=0.16-0.54) for Blacks, RR=0.26 (95%CI=0.09-0.74) for Hispanics, and RR=0.32 (95%CI=0.06-1.73) for Asians, comparing highest to lowest quartiles of SHBG. In addition, SHBG polymorphisms affected diabetes risk proportional to serum SHBG levels. Mendelian randomization analysis confirmed the significant direct effect of SHBG on diabetes development (p=0.03). CONCLUSIONS: In this prospective cohort of postmenopausal women, we observed a robust, inverse relation between serum levels of SHBG and clinical diabetes risk in American Blacks, Hispanics, and Asian/Pacific Islanders. Genetic variants associated with SHBG levels demonstrated a similar relationship, providing support for a causal role of SHBG in the pathogenesis of type 2 diabetes.

Relation of serum levels of sex hormone binding globulin to coronary heart disease in postmenopausal women

2002 ◽  
Vol 90 (4) ◽  
pp. 364-368 ◽  
Author(s):  
Holger Reinecke ◽  
Janina Bogdanski ◽  
Anne Woltering ◽  
G.ünter Breithardt ◽  
Gerd Assmann ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Postmenopausal Women ◽  
Serum Levels ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding

scholarly journals Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

Diabetes Care ◽  
2020 ◽  
pp. dc201137
Author(s):  
Tricia M. Peters ◽  
Michael V. Holmes ◽  
J. Brent Richards ◽  
Tom Palmer ◽  
Vincenzo Forgetta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Sex Differences ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

Abstract 23: Sexual Dimorphism In Genetic Associations Of Testosterone And Sex-hormone Binding Globulin With Coronary Heart Disease

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Jie Hu ◽  
Jun Li ◽  
Wonil Chung ◽  
Kathryn M Rexrode ◽  
Liming Liang
Keyword(s):  
Coronary Heart Disease ◽  
Sex Differences ◽  
Heart Disease ◽  
Genetic Correlation ◽  
Genetic Regulation ◽  
Genetic Correlations ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Specific Gene ◽  
Hormone Binding

Introduction: Men have higher prevalence and mortality of coronary heart disease (CHD) than women. Sex differences in associations of testosterone (T) and sex-hormone binding globulin (SHBG) with CHD risk have been recognized. But mechanisms underlying sex differences in CHD are unknown. Hypothesis: Genetic regulations of T and SHBG may differ by sex; such genetic heterogeneity may contribute to sex differences in CHD. Methods: We carried out a sex-stratified genome-wide association study for T, SHBG, and CHD in 187,888 men and 221,014 women from the UK Biobank, to identify sex-specific ( P <5х10 -8 in one sex and P ≥5х10 -8 in the other) and sex-differed ( P <5х10 -8 in both sexes but effects differed significantly by sex) loci for each trait. Plasma T and SHBG were measured by immunoassay. Genetic correlations were estimated using linkage disequilibrium score regressions. We used cross-traits meta-analyses to identify loci that coregulate a biomarker (T or SHBG) and CHD. Results: The median T levels in men were 10-12 times higher than that in women across all age groups. Women had higher SHBG levels. We identified 344 sex-specific/sex-differed loci for T and 89 for SHBG ( Fig. A ). Genetic correlations between sexes were 0.02 for T, suggesting mostly sex-specific genetic regulation, and were 0.86 for SHBG and 0.94 for CHD, suggesting partially sex-differed genetic regulation. We observed a significant inverse genetic correlation between T and CHD in men ( r g =-0.15; P =1.4х10 -5 ) but not in women. The inverse genetic correlation between SHBG and CHD was stronger in women ( r g =-0.33; P =5.2х10 -11 ) than men ( r g =-0.18; P =2.8х10 -7 ). We identified 31 sex-specific loci coregulating T and CHD (26 for men and 5 for women), and 48 sex-specific loci coregulating SHBG and CHD (35 for men and 13 for women) ( Fig. B ). Tissue-specific gene expression regulations at some loci (e.g. LPA ) were also differed by sex ( Fig. C ). Conclusions: The between-sex heterogeneity in genetic coregulations of T and SHBG with CHD may contribute to the sex-differences in CHD etiology.

scholarly journals Genetically predicted sex hormone binding globulin and ischemic heart disease in men and women: a univariable and multivariable Mendelian randomization study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie V. Zhao ◽  
C. Mary Schooling
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Mendelian Randomization ◽  
Sex Hormone ◽  
Ischemic Heart ◽  
Sex Hormone Binding Globulin ◽  
Inverse Association ◽  
Hormone Binding ◽  
The Uk

AbstractMen are more vulnerable to ischemic heart disease (IHD) than women, possibly due to testosterone. Correspondingly, sex hormone binding globulin (SHBG) which lowers circulating testosterone might protect men against IHD. SHBG may also affect IHD independent of testosterone, which has not previously been examined. To assess the sex-specific role of SHBG in IHD, in univariable Mendelian randomization (MR), we used sex-specific, genome-wide significant genetic variants to predict SHBG, and examined their association with IHD in the UK Biobank. We also replicated using genetic instruments from Japanese men and applied to Biobank Japan. To assess the role of SHGB independent of testosterone in men, we used multivariable MR controlling for testosterone. Genetically predicted SHBG was associated with lower IHD risk in men [odds ratio (OR) 0.78 per standard deviation, 95% confidence interval (CI) 0.70 to 0.87], and the association was less clear in women. The estimates were similar in Japanese. The inverse association remained after controlling for testosterone in men (OR 0.79, 95% CI 0.71 to 0.88). SHBG might lower the risk of IHD in men, with a role independent of testosterone. Exploring intervention strategies that increase SHBG is important for targeting IHD treatments.

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