Sex Differences in the Associations of Age-Related Genetic Predisposition With Incident Atrial Fibrillation: A Prospective Cohort Study.

A high AF polygenic risk score (top quintile, ≥0.858) was significantly associated with incident atrial fibrillation in a large UK Biobank cohort.

• Prospective cohort of 386,154 participants aged 40 to 69 years.
• Median follow-up was 15.6 years.
• High polygenic risk score was defined as ≥0.858 (top quintile).
• Cox regression was used to evaluate sex- and age-specific genetic effects.

The age-related trajectories of the polygenic risk score association with incident AF differed between men and women when age was modeled continuously.

• The abstract reports "P for difference in age-related trajectories=0.005".
• Analyses treated age as a continuous variable.

In participants aged 40 to 49 years, the hazard ratio for high polygenic risk score was numerically higher in men than in women, but the sex interaction was not significant after Bonferroni adjustment.

• HR was 2.76 in men versus 2.07 in women.
• Bonferroni-adjusted P for interaction = 0.077.

In participants aged 60 to 69 years, the association between high polygenic risk score and incident AF was significantly stronger in women than in men.

• HR was 2.22 in women versus 1.95 in men.
• Bonferroni-adjusted P for interaction <0.001.

Cross-validated prediction analyses showed broadly similar age- and sex-specific patterns to the hazard ratio analyses.

• Prediction performance was assessed with 10-fold cross-validated C-statistic and Royston's R2.
• Patterns across age and sex broadly paralleled the Cox regression findings.

The population-attributable risk percentage of high polygenic risk score showed different age patterns in men and women.

• In men, population-attributable risk gradually declined across age strata.
• In women, population-attributable risk first increased and then decreased across age strata.