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[Preprint]. 2025 Jul 14:2025.07.12.25331418.
doi: 10.1101/2025.07.12.25331418.

Genetic Ancestry and Risk of Atrial Fibrillation in Individuals of Black Ethnicity in the UK Biobank

Chang Liu  1 , Yan V Sun  1   2 , Linzi Li  1 , Lindsay J Collin  1 , Amit J Shah  1   2 , Alvaro Alonso  1
Affiliations

Genetic Ancestry and Risk of Atrial Fibrillation in Individuals of Black Ethnicity in the UK Biobank

Chang Liu et al. medRxiv. .

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.

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Figures

Figure 1.
Figure 1.
Distribution of European genetic ancestry among the UK Biobank participants self-reported as Black.
Figure 2.
Figure 2.
Flexible non-linear hazard ratio curves of the association between European genetic ancestry and incident AF among the UK Biobank participants self-reported as Black. Models adjusted for age at enrollment, sex (male vs. female), education (high [college or university degree; NVQ, HND, or HNC or equivalent, other professional qualifications] vs. low [ A levels / AS levels or equivalent, O levels / GCSEs or equivalent, CSEs or equivalent, none of the above] vs. missing), income (≤ £ 30,999 vs. ≥ £31,000 vs. missing), current smoking, body mass index, height, systolic blood pressure, diastolic blood pressure, blood pressure lowering medication use, prevalent type 2 diabetes, prevalent coronary artery disease, prevalent heart failure.
Figure 3.
Figure 3.
Association between genome-wide European ancestry and atrial fibrillation risk among Black adults across four cohorts. Panel A shows the fixed-effect meta-analysis; Panel B shows the random-effects meta-analysis. Relative risks (RRs) are per 10% increase in European ancestry.
See this image and copyright information in PMC

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