Abstract
AIMS: To study the association between an atrial fibrillation (AF) genetic risk score with prevalent AF and all-cause mortality in patients with heart failure. METHODS AND RESULTS: An AF genetic risk score was calculated in 3759 European ancestry individuals (1783 with sinus rhythm, 1976 with AF) from the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) by summing 97 single nucleotide polymorphism (SNP) alleles (ranging from 0-2) weighted by the natural logarithm of the relative SNP risk from the latest AF genome-wide association study. Further, we assessed AF risk variance explained by additive SNP variation, and performance of clinical or genetic risk factors, and the combination in classifying AF prevalence. AF was classified as AF or atrial flutter (AFL) at baseline electrocardiogram and/or a history of AF or AFL. The genetic risk score was associated with AF after multivariable adjustment. Odds ratio for AF prevalence per 1-unit increase genetic risk score was 2.12 (95% confidence interval 1.84-2.45, P = 2.15 × 10(-24) ) in the total cohort, 2.08 (1.72-2.50, P = 1.30 × 10(-14) ) in heart failure with reduced ejection fraction (HFrEF) and 2.02 (1.37-2.99, P = 4.37 × 10(-4) ) in heart failure with preserved ejection fraction (HFpEF). AF-associated loci explained 22.9% of overall AF SNP heritability. Addition of the genetic risk score to clinical risk factors increased the C-index by 2.2% to 0.721. CONCLUSIONS: The AF genetic risk score was associated with increased AF prevalence in HFrEF and HFpEF. Genetic variation accounted for 22.9% of overall AF SNP heritability. Addition of genetic risk to clinical risk improved model performance in classifying AF prevalence.