Genetically predicted body composition in relation to cardiometabolic traits: a Mendelian randomization study

Area of Science:

• Genetics
• Metabolic Health
• Cardiovascular Disease

Background:

• Observational studies suggest links between body composition (fat mass, fat-free mass) and cardiometabolic health, but causality is uncertain.
• Understanding these causal relationships is crucial for effective health management and risk stratification.

Purpose of the Study:

• To investigate the causal relationships between body composition (fat mass, fat-free mass, fat percentage) and cardiometabolic traits.
• To utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design.
• Utilized genetic variants from UK Biobank as instrumental variables for body composition traits.
• Estimated causal effects on cardiometabolic diseases, glycemic traits, and lipid fractions using large-scale GWAS data from European populations.

Main Results:

• Genetically predicted high fat mass and fat percentage were associated with increased risks of most cardiometabolic diseases.
• High fat-free mass demonstrated protective effects against most cardiometabolic diseases, independent of fat mass.
• Specific associations were found with atrial fibrillation, venous thromboembolism, glycemic control, and lipid profiles.

Conclusions:

• Body composition significantly influences cardiometabolic health through distinct causal pathways for fat mass and fat-free mass.
• Findings support targeted management of body composition for preventing and treating cardiometabolic diseases.
• This research aids in personalized risk stratification for individuals with varying cardiometabolic statuses.