Korean atrial fibrillation network genome-wide association study for early-onset atrial fibrillation identifies novel susceptibility loci

Abstract

Aims Some genetic susceptibility loci for atrial fibrillation (AF) identified by genome-wide association studies (GWAS) in a European database showed ethnic differences in the Asian population. We explored novel AF susceptibility variants for patients with early-onset AF (<= 60 years old) among Korean patients who underwent AF catheter ablation. Methods and results A genome-wide association study (GWAS) was conducted with 672 cases (<= 60 years old, Yonsei AF Ablation cohort) and 3700 controls (Korea Genome Epidemiology Study). Association analysis was performed under an additive model of logistic regression, and replication study was conducted with 200 independent cases of Korean AF Network and 1812 controls. Five previously proven genetic loci (1q24/PRRX1, 4q25/PITX2, 10q24/NEURL, 12q24/TBX5, and 16q22/ZFHX3) were validated. Two novel genetic loci associated with early-onset AF were found on chromosomes 1q32.1/PPFIA4 (rs11579055, P = 6.84 x 10(-10)) and 4q34.1/HAND2 (rs8180252, P = 1.49 x 10(-11)) and replicated in an additional independent sample of the Korean AF Network. The identified loci implicate candidate genes that encode proteins related to cell-to-cell connection, hypoxic status, or long non-coding RNA. Conclusion Two novel genetic loci for early-onset AF were identified in Korean patients who underwent catheter ablation. One of the novel susceptibility loci on chromosome 4 has strong associations with previously proven gene in a European ancestry database.