title: Common genetic variants and response to atrial fibrillation ablation.
abstract: BACKGROUND
  Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation.
  
  
  RESULTS
  Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1-1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence.
  
  
  CONCLUSIONS
  Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.). moore.b.shoemaker@vanderbilt.edu.
authors: M Benjamin
authors: MB
authors: Shoemaker
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Andreas
authors: A
authors: Bollmann
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Steven A
authors: SA
authors: Lubitz
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Laura
authors: L
authors: Ueberham
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Harsimran
authors: H
authors: Saini
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Jay
authors: J
authors: Montgomery
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Todd
authors: T
authors: Edwards
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Zachary
authors: Z
authors: Yoneda
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Moritz F
authors: MF
authors: Sinner
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Arash
authors: A
authors: Arya
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Philipp
authors: P
authors: Sommer
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Jessica
authors: J
authors: Delaney
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Sandeep K
authors: SK
authors: Goyal
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Pablo
authors: P
authors: Saavedra
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Arvindh
authors: A
authors: Kanagasundram
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: S Patrick
authors: SP
authors: Whalen
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Dan M
authors: DM
authors: Roden
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Gerhard
authors: G
authors: Hindricks
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Christopher R
authors: CR
authors: Ellis
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Patrick T
authors: PT
authors: Ellinor
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Dawood
authors: D
authors: Darbar
authors: From the Department of Medicine, Vanderbilt University, Nashville, TN (M.B.S., J.M., T.E., Z.Y., J.D., S.K.G., P.S., A.K., S.P.W., D.M.R., C.R.E., D.D.); Department of Electrophysiology, Heart Center Leipzig, Leipzig, Germany (A.B., L.U., A.A., P.S., G.H., D.H.); Cardiac Arrhythmia Service and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A.L., H.S., P.T.E.); and Department of Medicine, University Hospital Munich, Munich, Germany (M.F.S.).
authors: Daniela
authors: D
authors: Husser
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D001282:Atrial Flutter / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001900:Boston; D017115:Catheter Ablation / Q000009:adverse effects; D016009:Chi-Square Distribution; D002878:Chromosomes, Human, Pair 1; D002885:Chromosomes, Human, Pair 16; D002894:Chromosomes, Human, Pair 4; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012008:Recurrence; D012307:Risk Factors; D013617:Tachycardia, Supraventricular / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D013714:Tennessee; D013997:Time Factors; D016896:Treatment Outcome
keywords: ablation techniques; atrial fibrillation; genomics