Impact of a genetic risk score using common genetic variants on the response to atrial fibrillation catheter ablation

Abstract

Background: Genetic predisposition plays a substantial role in the development and progression of atrial fibrillation (AF). However, the association of AF susceptibility loci with recurrence after catheter ablation has been reported with controversial results. We sought to find out the impact of cumulative genetic risk score (GRS) on response to AF catheter ablation.

Methods: We determined the association between the 20 AF-susceptible single nucleotide polymorphisms (SNPs) and AF recurrence after catheter ablation in 746 patients (74% males

age, 59±11 years

56% paroxysmal AF). A GRS was calculated by summing the unweighted numbers of risk alleles of SNPs, which showed at least borderline significant association with AF recurrence. The primary outcome was AF recurrence after a 3-month blanking period. A Cox proportional hazard model was used to identify the association between the GRS and risk of AF recurrence after catheter ablation.

Results: During median 23 months of follow-up, 168 (23%) patients showed clinical recurrence. The GRS was calculated using 5 SNPs (rs1448818, rs2200733, rs6843082, rs6838973 at chromosome 4q25 [PITX2] and rs2106261 at chromosome 16q22 [ZFHX3]), which showed modest associations with AF recurrence. The GRS was significantly associated with AF recurrence (hazard ratio [HR] per each score, 1.14

95% confidence interval [CI] 1.04-1.24). Patients with high risks (GRS 6-10) showed HR of 1.50 (95% CI 1.06-2.11), compared to patients with low risk (GRS 0-5).

Conclusion: Our novel GRS using 5 AF-susceptible SNPs strongly associated with AF recurrence after catheter ablation, with patients with a high GRS being at particularly high risk.