ABSTRACT: Background: Various studies have reported associations between synuclein alpha (SNCA) polymorphisms and Parkinson's disease (PD) risk. However, the results are inconsistent. We conducted a comprehensive meta-analysis of the associations between SNCA single-nucleotide polymorphisms (SNPs) and PD risk in overall populations and subpopulations by ethnicity. Methods: Standard meta-analysis was conducted according to our protocol with a cutoff point of p < 0.05. To find the most relevant SNCA SNPs, we used a cutoff point of p < 1 × 10-5 in an analysis based on the allele model. In the subgroup analysis by ethnicity, we divided the overall populations into five ethnic groups. We conducted further analysis on the most relevant SNPs using dominant and recessive models to identify the contributions of heterozygotes and homozygotes regarding each SNP. Results: In our comprehensive meta-analysis, 24,075 cases and 22,877 controls from 36 articles were included. We included 16 variants in the meta-analysis and found 12 statistically significant variants with p < 0.05. After narrowing down the variants using the p < 1 × 10-5 cutoff, in overall populations, seven SNPs increased the risk of PD (rs2736990, rs356220, rs356165, rs181489, rs356219, rs11931074, and rs2737029, with odds ratios [ORs] of 1.22-1.38) and one SNP decreased the risk (rs356186, with an OR of 0.77). In the East Asian group, rs2736990 and rs11931074 increased the risk (with ORs of 1.22-1.34). In the European group, five SNPs increased the risk (rs356219, rs181489, rs2737029, rs356165, and rs11931074, with ORs of 1.26-1.37) while one SNP decreased the risk (rs356186, with an OR of 0.77). The heterozygotes and homozygotes contributed differently depending on the variant. Conclusions: In summary, we found eight SNCA SNPs associated with PD risk, which had obvious differences between ethnicities. Seven SNPs increased the risk of PD and one SNP decreased the risk in the overall populations. In the East Asian group, rs2736990 and rs11931074 increased the risk. In the European group, rs356219, rs181489, rs2737029, rs356165, and rs11931074 increased the risk while rs356186 decreased the risk. Variants with the highest ORs and allele frequencies in our analysis should be given priority when carrying out genetic screening.
