Genetic Variants Associated With Susceptibility to Atrial Fibrillation in a Japanese Population

Abstract Background Atrial fibrillation (AF) affects millions of individuals worldwide. The genome-wide association studies have identified robust genetic associations with AF. Methods We genotyped 5461 participants of Japanese ancestry for 11 AF-related loci and determined the effects of carrying different numbers of risk alleles on disease development and age at disease onset. The weighted genetic risk score (GRS) was calculated, and its ability to predict AF was determined. Results Six single-nucleotide polymorphisms—rs593479 (1q24 in PRRX1 ), rs1906617 (4q25 near PITX2 ), rs11773845 (7q31 in CAV1 ), rs6584555 (10q25 in NEURL ), rs6490029 (12q24 in CUX2 ), and rs12932445 (16q22 in ZFHX3 ) ( P −5 )—were confirmed as being associated with AF. Patients with a high total number of risk alleles (9-12) had a younger median age at onset of AF (58 years; 95% confidence interval [CI], 55-60 years) than those with a low total number (1-4) (63 years; 95% CI, 61-64 years) ( P  = 0.0015). We observed a 4.38-fold (95% CI, 3.69-5.19) difference in risk of AF between individuals with scores in the top and bottom quartiles of the GRS. Receiver operating characteristic analysis indicated an area under the curve of 0.641 (95% CI, 0.628-0.653; P Conclusions Six loci were validated as associated with AF in a Japanese population. This study suggests that a combination of common genetic markers modestly facilitates discrimination of AF. This is the first report, to our knowledge, to demonstrate that the age of onset of AF is affected by common risk alleles.