coffee consumption, cardiac structure and function, heart failure, oxidative stress, linkage disequilibrium score regression analysis, Mendelian randomization, Diseases of the circulatory (Cardiovascular) system, RC666-701

ObjectiveTo assess the causal relationship between coffee consumption and cardiac structure and function in elderly European populations using multiple genetic methodologies.MethodsLeveraging genome-wide association study (GWAS) data from elderly European populations, we conducted linkage disequilibrium score regression (LDSC), two-step Mendelian randomization (MR), and colocalization analyses to investigate genetic associations, causal relationships, and mediating effects among these factors. Robustness of findings was verified through comprehensive sensitivity analyses.ResultsLDSC regression analysis revealed positive genetic correlations between coffee consumption and cardiac parameters, excluding left ventricular (LV) ejection fraction and right ventricular (RV) ejection fraction. MR results demonstrated favorable associations between increased coffee consumption and cardiac parameters. After applying the Bonferroni adjustment to IVW analysis, as coffee consumption increased by each 1-cup/day, LV end-diastolic volume increased (β = 0.128; 95% CI: 0.043–0.212; P = 0.002), an increase in LV end-systolic volume (β = 0.143; 95% CI: 0.053–0.232; P = 0.001), an increase in RV end-diastolic volume (β = 0.200; 95% CI: 0.095–0.305; P