Abstract
BACKGROUND: Black individuals have a lower incidence of atrial fibrillation (AF) than White individuals, despite a higher burden of traditional risk factors. Prior studies have suggested that European genetic ancestry may contribute to this paradox, but findings have been inconsistent. METHODS: We examined the association between European genetic ancestry and incident AF among 6,920 UK Biobank (UKB) participants who self-identified as Black and were free of AF at baseline. European ancestry proportions were estimated by comparing participants to HapMap reference populations and were analyzed both continuously and categorically using Cox proportional hazards models. Non-linear associations were evaluated using flexible hazard ratio spline curves. We then conducted a meta-analysis combining these results with those from the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Women's Health Initiative (WHI). RESULTS: During a median follow-up of 13.7 years, 205 (3%) participants developed incident AF. Each 10% increase in European ancestry was nominally associated with increased AF risk (HR 1.07, 95% CI: 0.95-1.20), and individuals in the highest ancestry category had a higher AF incidence rate. Random-effects meta-analysis of all four cohorts yielded a pooled relative risk (RR) of 1.09 (95% CI: 0.99-1.21), with substantial heterogeneity largely driven by the WHI study. Excluding WHI resulted in a pooled estimate (RR 1.14, 95% CI: 1.05-1.23) without heterogeneity. CONCLUSION: Our findings suggest a modest association between European genetic ancestry and increased AF risk among admixed Black individuals. Future studies should confirm these results, explore underlying mechanisms, and assess their clinical implications.