Choi SH, Jurgens SJ, Weng LC, et al. - By performing this case-control study, researchers investigated if and how rare and common genetic variation contributes to atrial fibrillation (AF) risk in the general population. For this purpose, they utilized the UK Biobank. Participants were AF cases (n = 1,546) and controls (n = 41,593) of genetically determined white-European ancestry. Using the LDpred algorithm, a polygenic risk score for AF was estimated. A comparison of the contribution of AF polygenic risk score and loss-of-function (LOF) variants to AF risk was performed. A significant link between AF and rare LOF variants was noted in a single gene, TTN, in a study of 9,099 genes with sufficient LOF variant carriers. Experts observed a more significant link with AF when restricting to LOF variants positioned in exons highly expressed in cardiac tissue (TTN_LOF). Findings highlighted the contribution of both monogenic and polygenic factors to AF risk in the general population. While a substantial AF penetrance was conferred by rare TTN_LOF variants, a larger proportion of genetic susceptibility to AF was explained by the additive influence of many common variants.