title: Variant rs2200733 on chromosome 4q25 confers increased risk of atrial fibrillation: evidence from a meta-analysis.
abstract: BACKGROUND
  Several genome-wide association studies have identified rs2200733, a single-nucleotide polymorphism (SNP) at 4q25 to be the most common chromosomal variant present in patients with atrial fibrillation (AF). We aimed to explore the association of rs2200733 with AF through a systematic review and meta-analysis.
  
  
  METHODS
  An extensive literature search was performed on PubMed, and other databases using the key words "genetics" and "AF." Seven case-control studies evaluating the association via multivariate analysis were identified including a total of 83,335 subjects (10,546 with AF, 72,789 referent individuals without AF). Meta-analytic estimates were derived using random effects models. Potential sources of heterogeneity were examined in sensitivity analyses, and publication biases were estimated.
  
  
  RESULTS
  At pooled analysis, there was a strong independent association between the variant rs2200733 and the risk of AF (OR 1.89 [95% CI 1.62-2.16], P < 0.001). Minor allelic frequencies for SNP rs22000733 were significantly more prevalent in AF population than non-AF. Metaregression results revealed that country of descent (logOR 0.38, P = 0.45) or site of study (logOR: -0.16, P = 0.41) did not moderate the overall effect size.
  
  
  CONCLUSIONS
  Variant rs2200733 on chromosome 4q25 independently confers increased risk of AF. This finding will aid in improving our understanding of AF pathophysiology, risk prediction, and stratification of treatment strategy.
authors.affiliation: St. David's Medical Center, Texas Cardiac Arrhythmia Institute, Austin, Texas 78705, USA.
authors.forename: Sanghamitra
authors.initials: S
authors.lastname: Mohanty
authors.forename: Pasquale
authors.initials: P
authors.lastname: Santangeli
authors.forename: Rong
authors.initials: R
authors.lastname: Bai
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Biase
authors.forename: Prasant
authors.initials: P
authors.lastname: Mohanty
authors.forename: Agnes
authors.initials: A
authors.lastname: Pump
authors.forename: Andrea
authors.initials: A
authors.lastname: Natale
mesh_terms: D001281:Atrial Fibrillation / Q000453:epidemiology* / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D019317:Evidence-Based Medicine; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors