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Article Abstract

Background: Early detection and management of atrial fibrillation (AF) are crucial. Combined models incorporating genetic risks and clinical risks have been developed to improve predictive ability. Although sex differences have been reported in many aspects of AF, sex differences in genetic risk have not been studied.

Objective: The purpose of this study was to assess the sex difference in the effect of polygenic risk score for AF (AF-PRS) on AF prevalence using cross-sectional data from the Tohoku Medical Megabank Project Community-Based Cohort Study in Japan.

Methods: AF-PRS and Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation (CHARGE-AF) score were used for genetic AF risks and clinical AF risks, respectively. Sex differences in the association of AF-PRS with the prevalence of AF were evaluated.

Results: Among 16,853 participants (mean age 63.4 years; 5182, 30.7% men), the prevalence of AF was 255 (4.9%) in men and 130 (1.1%) in women. In the group with high AF-PRS and high CHARGE-AF score, the odds ratio for AF was highest in men and women (8.2 in men and 9.4 in women), compared with that in the group with low AF-PRS and low CHARGE-AF score. Integrating AF-PRS into the CHARGE-AF score significantly enhanced the area under the receiver operating characteristic curve for AF in men (from 0.639 to 0.749) but not in women (from 0.710 to 0.733).

Conclusion: Our study is the first to show a sex difference in the association of AF-PRS and AF prevalence. AF-PRS is more closely associated with the prevalence of AF in men than in women.

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http://dx.doi.org/10.1016/j.hrthm.2025.03.1974DOI Listing

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