Sex Differences in the Associations of Age‐Related Genetic Predisposition With Incident Atrial Fibrillation: A Prospective Cohort Study
5 affiliations
- 1The First Affiliated Hospital of Anhui Medical University
- 2The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University)
- 3Anqing Medical Center of Anhui Medical University
- 4The Second Affiliated Hospital of Anhui Medical University
- 5Fuyang Infectious Disease Clinical College of Anhui Medical University
Abstract
Background Polygenic risks for diseases are age‐dependent. However, sex differences in the age‐related association between polygenic risk score and incident atrial fibrillation (AF) remain unclear. Methods A prospective cohort study was conducted using UK Biobank data, including 386 154 participants aged 40 to 69 years, with a median follow‐up of 15.6 years. High AF polygenic risk score was defined as ≥0.858 (top quintile). Cox regression, 10‐fold cross‐validated C‐statistic, Royston's R 2 , and population‐attributable risk percentages were used to evaluate sex‐ and age‐specific genetic effects on incident AF. Results High polygenic risk score was significantly associated with incident AF, and continuous‐age analyses showed that the age‐related trajectories differed across sexes ( P for difference in age‐related trajectories=0.005). In age‐stratified analyses, the association was numerically higher in men aged 40 to 49 years (hazard ratio [HR], 2.76 versus 2.07 in women; Bonferroni‐adjusted P for interaction=0.077), whereas it was higher in women aged 60 to 69 years (HR, 2.22 versus 1.95 in men; Bonferroni‐adjusted P for interaction <0.001). Cross‐validated prediction analyses showed broadly similar age‐ and sex‐specific patterns. Population‐attributable risk of high polygenic risk score gradually declined across age strata in men, whereas it first increased and then decreased in women. Conclusions Age‐related genetic predisposition to AF exhibits distinct sex‐specific patterns, offering a foundation for personalized risk stratification and prevention strategies tailored to age and sex.
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BibTeX
@article{zhang2026differences,
title = {{Sex Differences in the Associations of Age‐Related Genetic Predisposition With Incident Atrial Fibrillation: A Prospective Cohort Study}},
author = {Feilong Zhang and Yuhao Hu and Liangchuan Chen and Pengfei Zheng and Yangye Xu and Chi Yuan and Zhou Du and Yangjing Xie and Zhenhua Lu and Xiaochen Wang and Zhen Dong and Ronghui Yu},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.049774},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.049774},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Sex Differences in the Associations of Age‐Related Genetic Predisposition With Incident Atrial Fibrillation: A Prospective Cohort Study
AU - Feilong Zhang
AU - Yuhao Hu
AU - Liangchuan Chen
AU - Pengfei Zheng
AU - Yangye Xu
AU - Chi Yuan
AU - Zhou Du
AU - Yangjing Xie
AU - Zhenhua Lu
AU - Xiaochen Wang
AU - Zhen Dong
AU - Ronghui Yu
PY - 2026
DA - 2026/10/23
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.049774
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.049774
AB - Background Polygenic risks for diseases are age‐dependent. However, sex differences in the age‐related association between polygenic risk score and incident atrial fibrillation (AF) remain unclear. Methods A prospective cohort study was conducted using UK Biobank data, including 386 154 participants aged 40 to 69 years, with a median follow‐up of 15.6 years. High AF polygenic risk score was defined as ≥0.858 (top quintile). Cox regression, 10‐fold cross‐validated C‐statistic, Royston's R 2 , and population‐attributable risk percentages were used to evaluate sex‐ and age‐specific genetic effects on incident AF. Results High polygenic risk score was significantly associated with incident AF, and continuous‐age analyses showed that the age‐related trajectories differed across sexes ( P for difference in age‐related trajectories=0.005). In age‐stratified analyses, the association was numerically higher in men aged 40 to 49 years (hazard ratio [HR], 2.76 versus 2.07 in women; Bonferroni‐adjusted P for interaction=0.077), whereas it was higher in women aged 60 to 69 years (HR, 2.22 versus 1.95 in men; Bonferroni‐adjusted P for interaction <0.001). Cross‐validated prediction analyses showed broadly similar age‐ and sex‐specific patterns. Population‐attributable risk of high polygenic risk score gradually declined across age strata in men, whereas it first increased and then decreased in women. Conclusions Age‐related genetic predisposition to AF exhibits distinct sex‐specific patterns, offering a foundation for personalized risk stratification and prevention strategies tailored to age and sex.
SN - 2047-9980
ER -