Polygenic Risk of New Onset Atrial Fibrillation in Nonischemic Cardiomyopathy.

Area of Science:

• Cardiovascular Genetics
• Genomic Epidemiology
• Clinical Cardiology

Background:

• Polygenic risk scores (PRS) for atrial fibrillation (AF) are established predictors in general and cardiovascular disease populations.
• The utility of PRS for predicting new onset AF (NOAF) in nonischemic cardiomyopathy (NICM) patients is currently unknown.

Purpose of the Study:

• To evaluate the effectiveness of an AF-specific polygenic risk score (PRS_AF) in improving NOAF risk stratification within an NICM cohort.
• To assess the predictive performance of PRS_AF alone and in combination with established clinical risk scores.

Main Methods:

• A cohort of 2,661 participants with NICM and no prior AF diagnosis was established from the UK Biobank.
• PRS_AF was calculated to define polygenic risk, and the CHARGE-AF score was used for clinical risk assessment.
• Cox regression and time-dependent AUC analyses were employed to evaluate PRS_AF's predictive capability for NOAF.

Main Results:

• During a median follow-up of 55 months, 636 (23.9%) participants developed NOAF.
• Higher PRS_AF was significantly associated with increased NOAF risk (HR per 1 SD: 1.30), with the top 10th percentile showing a 1.91-fold increased likelihood of NOAF over 20 years.
• PRS_AF improved the predictive performance of clinical risk models, demonstrating enhanced risk stratification capabilities.

Conclusions:

• PRS_AF is a significant risk factor for NOAF in patients with NICM.
• Incorporating PRS_AF into clinical risk assessment tools can enhance the prediction and stratification of NOAF risk in this patient population.