Variant rs2200733 on Chromosome 4q25 Confers Increased Risk of Atrial Fibrillation: Evidence From a Meta‐Analysis

INTRODUCTION: 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. METHOD: 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. RESULT: 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. CONCLUSION: 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.