A genetic risk score for atrial fibrillation predicts the response to catheter ablation

Won Seok Choe, Jun Hyuk Kang, Eue Keun Choi, Seung Yong Shin, Steven A. Lubitz, Patrick T. Ellinor, Seil Oh, Hong Euy Lim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Objectives: The association of susceptibility loci for atrial fibrillation (AF) with AF recurrence after ablation has been reported, although with controversial results. In this prospective cohort analysis, we aimed to investigate whether a genetic risk score (GRS) can predict the rhythm outcomes after catheter ablation of AF. Methods: We determined the association between 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 selected SNPs. A Cox proportional hazard model was used to identify the association between the GRS and risk of AF recurrence after catheter ablation. Results: AF recurrences after catheter ablation occurred in 168 (22.5%) subjects with a median follow-up of 23 months. 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, 1.13; 95% confidence interval [CI], 1.03-1.24). Patients with intermediate (GRS 4-6) and high risks (GRS 7-10) showed HRs of 2.00 (95% CI, 0.99-4.04) and 2.66 (95% CI, 1.32-5.37), respectively, compared to patients with low risk (GRS 0-3). Conclusions: Our novel GRS using 5 AF-susceptible SNPs was strongly associated with AF recurrence after catheter ablation in Korean population, beyond clinical risk factors. Further efforts are warranted to construct a generalizable, robust genetic prediction model which can guide the optimal treatment strategies.

Original languageEnglish
Pages (from-to)338-349
Number of pages12
JournalKorean Circulation Journal
Volume49
Issue number4
DOIs
StatePublished - 1 Jan 2019

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Catheter Ablation
Atrial Fibrillation
Recurrence
Single Nucleotide Polymorphism
Confidence Intervals
Chromosomes
Genetic Models
Proportional Hazards Models
Cohort Studies

Keywords

  • Atrial fibrillation
  • Catheter ablation
  • Genetics
  • Recurrence

Cite this

Choe, W. S., Kang, J. H., Choi, E. K., Shin, S. Y., Lubitz, S. A., Ellinor, P. T., ... Lim, H. E. (2019). A genetic risk score for atrial fibrillation predicts the response to catheter ablation. Korean Circulation Journal, 49(4), 338-349. https://doi.org/10.4070/kcj.2018.0161
Choe, Won Seok ; Kang, Jun Hyuk ; Choi, Eue Keun ; Shin, Seung Yong ; Lubitz, Steven A. ; Ellinor, Patrick T. ; Oh, Seil ; Lim, Hong Euy. / A genetic risk score for atrial fibrillation predicts the response to catheter ablation. In: Korean Circulation Journal. 2019 ; Vol. 49, No. 4. pp. 338-349.
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abstract = "Background and Objectives: The association of susceptibility loci for atrial fibrillation (AF) with AF recurrence after ablation has been reported, although with controversial results. In this prospective cohort analysis, we aimed to investigate whether a genetic risk score (GRS) can predict the rhythm outcomes after catheter ablation of AF. Methods: We determined the association between 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 selected SNPs. A Cox proportional hazard model was used to identify the association between the GRS and risk of AF recurrence after catheter ablation. Results: AF recurrences after catheter ablation occurred in 168 (22.5{\%}) subjects with a median follow-up of 23 months. 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, 1.13; 95{\%} confidence interval [CI], 1.03-1.24). Patients with intermediate (GRS 4-6) and high risks (GRS 7-10) showed HRs of 2.00 (95{\%} CI, 0.99-4.04) and 2.66 (95{\%} CI, 1.32-5.37), respectively, compared to patients with low risk (GRS 0-3). Conclusions: Our novel GRS using 5 AF-susceptible SNPs was strongly associated with AF recurrence after catheter ablation in Korean population, beyond clinical risk factors. Further efforts are warranted to construct a generalizable, robust genetic prediction model which can guide the optimal treatment strategies.",
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A genetic risk score for atrial fibrillation predicts the response to catheter ablation. / Choe, Won Seok; Kang, Jun Hyuk; Choi, Eue Keun; Shin, Seung Yong; Lubitz, Steven A.; Ellinor, Patrick T.; Oh, Seil; Lim, Hong Euy.

In: Korean Circulation Journal, Vol. 49, No. 4, 01.01.2019, p. 338-349.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genetic risk score for atrial fibrillation predicts the response to catheter ablation

AU - Choe, Won Seok

AU - Kang, Jun Hyuk

AU - Choi, Eue Keun

AU - Shin, Seung Yong

AU - Lubitz, Steven A.

AU - Ellinor, Patrick T.

AU - Oh, Seil

AU - Lim, Hong Euy

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background and Objectives: The association of susceptibility loci for atrial fibrillation (AF) with AF recurrence after ablation has been reported, although with controversial results. In this prospective cohort analysis, we aimed to investigate whether a genetic risk score (GRS) can predict the rhythm outcomes after catheter ablation of AF. Methods: We determined the association between 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 selected SNPs. A Cox proportional hazard model was used to identify the association between the GRS and risk of AF recurrence after catheter ablation. Results: AF recurrences after catheter ablation occurred in 168 (22.5%) subjects with a median follow-up of 23 months. 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, 1.13; 95% confidence interval [CI], 1.03-1.24). Patients with intermediate (GRS 4-6) and high risks (GRS 7-10) showed HRs of 2.00 (95% CI, 0.99-4.04) and 2.66 (95% CI, 1.32-5.37), respectively, compared to patients with low risk (GRS 0-3). Conclusions: Our novel GRS using 5 AF-susceptible SNPs was strongly associated with AF recurrence after catheter ablation in Korean population, beyond clinical risk factors. Further efforts are warranted to construct a generalizable, robust genetic prediction model which can guide the optimal treatment strategies.

AB - Background and Objectives: The association of susceptibility loci for atrial fibrillation (AF) with AF recurrence after ablation has been reported, although with controversial results. In this prospective cohort analysis, we aimed to investigate whether a genetic risk score (GRS) can predict the rhythm outcomes after catheter ablation of AF. Methods: We determined the association between 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 selected SNPs. A Cox proportional hazard model was used to identify the association between the GRS and risk of AF recurrence after catheter ablation. Results: AF recurrences after catheter ablation occurred in 168 (22.5%) subjects with a median follow-up of 23 months. 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, 1.13; 95% confidence interval [CI], 1.03-1.24). Patients with intermediate (GRS 4-6) and high risks (GRS 7-10) showed HRs of 2.00 (95% CI, 0.99-4.04) and 2.66 (95% CI, 1.32-5.37), respectively, compared to patients with low risk (GRS 0-3). Conclusions: Our novel GRS using 5 AF-susceptible SNPs was strongly associated with AF recurrence after catheter ablation in Korean population, beyond clinical risk factors. Further efforts are warranted to construct a generalizable, robust genetic prediction model which can guide the optimal treatment strategies.

KW - Atrial fibrillation

KW - Catheter ablation

KW - Genetics

KW - Recurrence

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DO - 10.4070/kcj.2018.0161

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