Abstract 10896: Six Chromosome Loci for Atrial Fibrillation Susceptibility Identified in the Japanese Population
Development and progression of atrial fibrillation (AF) depends on complex interactions of multiple environmental and genetic factors. Several chromosomal loci associated AF were identified by means of genome wide association study (GWAS) using single nucleotide polymorphisms, so far. We recently reported in silico replication study for Caucasian descent by a GWAS results with 843 cases and 3,350 controls in a Japanese population1). In this analysis, the locus corresponding to the SNPs close to PITX2 on chromosome 4q25 only satisfied a genome wide significance, however, other three loci modestly associated with risk of AF in the Japanese population. Here, to further validate the results of the Japanese GWAS and to identify novel AF susceptible loci, we genotyped the high-ranking SNPs in the GWAS with additional samples of approximately 1,600 cases and 17,100 controls in the Japanese population. Through combination of the GWAS and this validation study, known three loci, CAV1, 2 locus on 7q31, ZFHX3 locus on 16q22 and PRRX1 locus on 1q24, were further validated with strong statistical significance (P < 1.0 x 10-8) as AF loci for the Japanese population in addition to 4q25. Furthermore, we identified two novel association signal on chromosome 10 and 12 (P < 5 x 10-8). Interestingly, the four genes (PITX2, PRRX1, ZFHX3 and the gene on chromosome 12) encode transcription related factors with homeobox domain found in proteins related to cardiopulmonary development and/or differentiation. Stratification by age at diagnosis revealed that the greater odds ratios observed in the younger age than the older one on the three loci, PITX2, CAV1, 2 and chromosome 12. By combination of the six genetic risk factors for Japanese population, the odds ratio has risen to about 6. These results indicate that the genetic risk factors significantly contribute to the development and/or progression of AF in the Japanese population. 1)Ellinor PT et al., Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nature Genetics 44, 670-675 (2012).
- © 2012 by American Heart Association, Inc.