Cardiology · Medical Literature
Genetic ancestry and risk of atrial fibrillation in individuals of Black ethnicity in the UK Biobank.
Abstract
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. We examined the association between European genetic ancestry and incident AF among 6920 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 populations and were analysed both continuously and categorically using Cox proportional hazards models. Non-linear associations were evaluated using flexible 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. During a median follow-up of 13.7 years, 205 (3%) participants developed incident AF. Each 10% increase in European ancestry was non-significantly associated with increased AF risk (HR 1.07 (95% CI 0.95 to 1.20)), and individuals in the highest European ancestry category had a higher AF incidence rate compared with all other categories. Random-effects meta-analysis of all four cohorts yielded a pooled relative risk (RR) of 1.09 (95% CI 0.99 to 1.21), with substantial heterogeneity largely driven by the Women's Health Initiative (WHI) study. Excluding WHI resulted in a pooled estimate (RR 1.14 (95% CI 1.05 to 1.23)) without heterogeneity. In UKB, European ancestry proportion was not significantly linked to incident AF, and pooled cross-cohort results were heterogeneous. Excluding WHI in sensitivity analyses produced a modest positive pooled association with no heterogeneity.
Clinical relevance
Atrial fibrillation (AF) exhibits a well-documented epidemiological paradox in which Black individuals have a lower AF incidence than White individuals despite carrying a higher burden of traditional cardiovascular risk factors such as hypertension and obesity. This study addresses the hypothesis that European genetic ancestry may partially explain this disparity, examining 6,920 self-identified Black UK Biobank participants—a question with direct implications for risk stratification and health equity in cardiology. Understanding the genetic underpinnings of AF risk across ancestral groups is increasingly relevant as polygenic risk scores and ancestry-informed medicine enter clinical practice.
Key findings
1. Among 6,920 self-identified Black UK Biobank participants free of AF at baseline, 205 (3%) developed incident AF over a median follow-up of 13.7 years. 2. Each 10% increment in European genetic ancestry proportion was associated with a non-significant increase in AF risk (HR 1.07, 95% CI 0.95–1.20) in the UK Biobank cohort alone. 3. Individuals in the highest European ancestry category demonstrated a higher AF incidence rate compared with all other ancestry categories in the UK Biobank. 4. Random-effects meta-analysis pooling results from the UK Biobank, Atherosclerosis Risk in Communities Study (ARIC), Cardiovascular Health Study (CHS), and Women's Health Initiative (WHI) yielded a pooled RR of 1.09 (95% CI 0.99–1.21), which did not reach statistical significance and was accompanied by substantial between-cohort heterogeneity. 5. Heterogeneity across cohorts was largely driven by the WHI study; excluding WHI in a sensitivity analysis produced a pooled RR of 1.14 (95% CI 1.05–1.23) that reached statistical significance and was free of significant heterogeneity. 6. Non-linear association between European ancestry proportion and AF risk was evaluated using flexible spline curves, though no definitive non-linear threshold was reported in the abstract.
Practice implications
Clinicians should not use European genetic ancestry proportion as a standalone clinical tool for AF risk stratification in Black patients at this time, given the modest, heterogeneous, and largely non-significant associations observed across cohorts. The finding that higher European ancestry may confer modestly increased AF risk (RR ~1.14 in the most consistent sensitivity analysis) supports continued investigation into ancestry-informed polygenic risk scores for AF, but current evidence is insufficient to alter screening thresholds or preventive strategies by ancestry subgroup. In the interim, clinicians should prioritize aggressive management of traditional, modifiable AF risk factors—particularly hypertension, obesity, and sleep apnea—in all Black patients, irrespective of genetic ancestry, given the already elevated cardiovascular risk burden in this population.