In addition, with the increased studies in recent years among Asian, and other populations, there is a need to reconcile these data. We therefore performed a meta-analysis of the published studies to clarify this inconsistency and to establish a comprehensive picture of the relationship between genetic markers of chromosome 9p21 and IS. Genome-wide association studies have identified a locus for risk of coronary artery disease on chromosome 9p21. Recent studies have also analyzed the association between 9p21 and overall ischemic stroke, with diverse outcomes. The present meta-analysis provides the most comprehensive assessment of the risk of IS and 9p21 variant. Its strength was based on the accumulation of published data giving greater information to detect significant differences. In total, the metaanalysis involved 21 studies for IS which provided 34,128 cases and 153, 428 controls. Our results demonstrated that the rs10757278 polymorphism on chromosome 9p21 is a risk factor for developing ischemic stroke. In the stratified analysis by ethnicity, significant associations were found in East Asian and Caucasian populations for the polymorphism in all genetic models. However, no significant associations were detected among African populations. There are several possible reasons for such differences. In fact, the frequencies of the risk-association GDC-0449 879085-55-9 alleles in chromosome 9p21 are similar in European and East Asian populations, but substantially lower in African descent. Thus, failing to identify any significant association in African populations could be due to substantially lower statistical power caused by the relatively lower prevalence of the risk allele. In addition, study design or small sample size or some environmental factors may affect the results. Most of these studies did not consider most of the important environmental factors. It is possible that variation at this locus has modest effects on IS, but environmental factors may predominate in the progress of IS, and mask the effects of this variation. Specific environmental factors like lifestyle and diabetes that have been already well studied in recent decades. The unconsidered factors mixed together may cover the role of the polymorphism. Furthermore, different populations usually have different linkage disequilibrium patterns. A polymorphism may be in close linkage with another nearby causal variant in one ethnic population but not in another. The rs10757278 polymorphism may be in close linkage with different nearby causal variants in different populations. Nevertheless, owing to the limited number of relevant studies among African Americans included in this meta-analysis, the observed ethnic difference in this meta-analysis is also likely to be caused by chance because studies with small sample sizes may have insufficient statistical power to detect a slight effect or may have generated a fluctuated risk estimate. Meta-analysis is often dominated by a few large studies, which markedly reduces the evidence from smaller studies.