Figure 6.

The figure summarizes the identified genetic associations of atrial fibrillation (AF) and future areas of genetic study. Investigators have identified Mendelian families with AF genes having large effect size but rare frequency. Both candidate gene studies and genome-wide association studies (GWAS) have identified variants and loci with low-to-modest effect sizes. Among the two study types, candidate gene studies have tended to report larger effect sizes. Such an overestimation of effect size has been described in a phrase borrowed from economics as the “winner’s curse.” In contrast GWAS have identified three distinct loci with low-to-modest effect sizes. Sequencing efforts may fill a substantive genomic gap by identifying unrecognized low-frequency variants with moderate effect sizes. As a prominent component of the population attributable risk (see Figure 3) remains unknown, further genetic study may contribute additional insights into the etiology of AF. Figure modified from Manolio et al.¹²¹