Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study

Area of Science:

• Genetics and Cardiovascular Medicine
• Adipokine Research
• Mendelian Randomization Studies

Background:

• Observational studies suggest links between adipokines and cardiovascular disease (CVD), but causal relationships remain unclear.
• Specific roles of adipokines like adiponectin, resistin, chemerin, and RBP4 in CVD are debated.

Purpose of the Study:

• To determine if circulating adipokines causally influence the risk of various cardiovascular diseases (CVD).
• Utilized a 2-sample Mendelian randomization (MR) approach to assess causality.

Main Methods:

• Selected genetic variants associated with adiponectin, resistin, chemerin, and RBP4 from GWAS.
• Collected summary-level data for CVD outcomes including coronary artery disease (CAD), myocardial infarction, atrial fibrillation (AF), heart failure (HF), and stroke.
• Employed inverse-variance weighted and Wald ratio methods for MR analysis, with comprehensive sensitivity analyses for pleiotropy.

Main Results:

• Genetically predicted resistin showed a positive association with AF risk, which diminished after adjusting for blood pressure.
• Suggestive evidence linked higher genetically predicted chemerin to increased CAD risk.
• Higher genetically predicted RBP4 levels were associated with an increased risk of HF.
• No causal association was found between adiponectin and CVD risk.

Conclusions:

• Resistin appears to have a causal association with AF, likely mediated by blood pressure.
• Chemerin and RBP4 may have potential causal roles in CAD and HF, respectively.
• Adiponectin is unlikely to have a causal effect on the studied CVD outcomes.