Evaluating Polygenic Risk Scores in “Lone” Atrial Fibrillation

Abstract Background Polygenic scores incorporating varying numbers of single nucleotide polymorphisms (SNPs) have been demonstrated to exert a prominent role in atrial fibrillation (AF). We sought to compare the relative discriminatory capacities of 2 previously validated polygenic scores in “lone” AF. Methods A total of 186 “lone” AF cases of European ancestry underwent SNP genotyping. A genome-wide polygenic score (GPS) and polygenic risk score (PRS) involving 6,730,541 and 1,168 SNPs, respectively, were calculated for 186 cases and 423 controls of European ancestry from the 1000 Genomes (1KG) Project. The distribution of the polygenic scores was compared between the cases and controls and their discriminatory capacities were evaluated using receiver operating characteristic (ROC) curves. Results A total of 34.4% of “lone” AF patients had GPS scores greater than the top 10th percentile of 1KG controls, corresponding to a 4.64-fold increased odds (95% confidence interval (CI) [2.99-7.18]; p Conclusion Our study evaluating 2 polygenic scores for AF suggests that the GPS, containing over 6.7 million SNPs, exhibits an improved discriminatory capacity in “lone” AF compared to a PRS possessing 1,168 SNPs. Our findings suggest that genetic risk scores for AF that maximally leverage genomic data may provide improved predictive power.