Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian...

Area of Science:

• Genetics
• Cardiovascular Medicine
• Endocrinology

Background:

• Observational studies suggest an inverse relationship between serum sex hormone-binding globulin (SHBG) and coronary heart disease (CHD) risk.
• Dyslipidemia is a known risk factor for CHD, prompting investigation into potential mediating pathways.

Purpose of the Study:

• To confirm the mediating role of blood lipid levels in the association between SHBG and CHD using Mendelian randomization (MR) and mediation analysis.
• To assess the causal relationship between SHBG levels and cardiovascular diseases.

Main Methods:

• Univariable Mendelian randomization (MR) was used to evaluate causality between serum SHBG levels and five cardiovascular diseases.
• Mediation analysis was employed to quantify the proportion of the SHBG-CHD association mediated by blood lipid levels.
• Genome-wide association study (GWAS) summary-level data from UK Biobank and meta-analyses were utilized.

Main Results:

• Serum SHBG levels showed a causal effect in reducing the risk of CHD, myocardial infarction, and hypertension.
• A significant inverse association was found between SHBG and CHD risk (OR 0.73 per SD increase).
• Mediation analysis indicated that high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%) significantly mediated the effect of SHBG on CHD risk.

Conclusions:

• Serum SHBG has a protective causal effect against CHD, myocardial infarction, and hypertension.
• The reduction in CHD risk associated with higher SHBG levels is substantially mediated by improvements in blood lipid profiles.