Related Experiment Video
Updated: Jan 16, 2026

Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Sex Differences in the Association Between Polygenic Risk Score and Atrial Fibrillation Incidence: A Prospective
Feilong Zhang1, Yuhao Hu1, Jinfeng Wang1
1Department of Cardiology, National Cardiovascular Disease Regional Center for Anhui, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Background:
Although sex disparities in atrial fibrillation (AF) epidemiology and outcomes are well documented, the role of sex in modulating genetic susceptibility to incident AF remains poorly characterized. In this study we assessed sex-specific effects of polygenic risk score (PRS) on AF incidence and the sex-specific PRS effects, stratified by the Cohorts for Heart and Aging Research in Genomic Epidemiology for Atrial Fibrillation (CHARGE-AF) clinical risk score.
Methods:
This prospective cohort study included 444,463 AF-free UK Biobank participants (54.67% women; mean age 56.46 ± 8.09 years). Participants were stratified by sex, AF-PRS (cutoff ≥ 0.295), and CHARGE-AF clinical risk score (cutoff ≥ 12.048). Incident AF was ascertained via ICD-10 codes. Cox hazards regression (adjusting for clinical, metabolic, lifestyle, and socioeconomic covariables) was used to evaluate the multiplicative interactions among AF-PRS, sex, and CHARGE-AF.
Results:
Over 14.67 ± 3.01 years, 31,070 participants experienced incident AF. A significant interaction between male sex and higher AF-PRS emerged (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.91-1.00; P = 0.031). Women were more genetically susceptible to AF at higher CHARGE-AF (HR 1.99 vs 1.83 in men) and men at lower CHARGE-AF (HR 2.33 vs 2.11 in women). In addition, the tripartite interaction (AF-PRS × sex × CHARGE-AF, HR 0.84; P < 0.001) further validated the sex-specific results stratified by CHARGE-AF.
Conclusions:
The association between AF-PRS and incident AF is modified by sex, with clinical risk burden modifying sex-related PRS effects. Women presented with higher genetic susceptibility at higher CHARGE-AF, and men at lower CHARGE-AF. Rethinking AF genetic susceptibility in a sex- and context-dependent manner may enhance precise prevention.
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Polygenic Traits
Bias in Epidemiological Studies
Relative Risk
Confounding in Epidemiological Studies
Odds Ratio

