ArticleScientific reports2024
Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The Sex-Stratified Effects of RSPO3 Expression on Body Fat and Blood Lipids: An Omics Mendelian Randomization Study.Obesity (Silver Spring, Md.) · 2026Article
- Construction and validation of a diagnostic model for obstructive coronary artery disease in patients with suspected unstable angina pectoris based on restingQuantitative imaging in medicine and surgery · 2026Article
- Heterogeneity of effect of Intensive lifestyle intervention on cardiometabolic risk factors by sex hormones in diabetes.medRxiv : the preprint server for health sciences · 2025Article
- Causal relationship between immune cells and osteoporosis based on genetic prediction: a bidirectional two-sample mediated Mendelian randomization analysis.Scientific reports · 2025Article
- Association of ultra-processed food-related metabolites with selected biochemical markers in the UK Biobank.Nutrition journal · 2025Article
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Authors and funding
9 authors.
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Abstract
Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.
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