Variant rs2200733 on Chromosome 4q25 Confers Increased Risk.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 1.622.16], 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. (J Cardiovasc Electrophysiol, Vol. 24, pp. 155-161, February 2013)