Common SNCA Genetic Variants and Parkinson's Disease Risk: A Systematic Review and Meta-Analysis

The SNCA gene, encoding alpha-synuclein, is implicated in the pathogenesis of Parkinson's disease (PD), with several single-nucleotide polymorphisms (SNPs) linked to increased risk. This study systematically evaluated the association between common SNCA polymorphisms and PD through a meta-analysis of cohort and case-control studies published before 20 November 2023. Eligible studies were identified via comprehensive searches of PubMed, Scopus, and Web of Science, and pooled odds ratios with 95% confidence intervals were calculated under allelic, dominant, and recessive models. Heterogeneity and publication bias were assessed, and subgroup and sensitivity analyses were performed. Twenty-seven studies were included. SNP rs11931074 showed consistent associations with PD across all models, with low heterogeneity and no evidence of publication bias. rs356219 and rs356165 were also significantly associated with PD, although regional differences contributed to heterogeneity. In contrast, rs2583988 showed marginal significance in the allelic model, which was lost after sensitivity analyses. No associations were found under dominant or recessive models for this SNP. These findings confirm rs11931074 as a robust PD risk variant and support the roles of rs356219 and rs356165 while suggesting weaker evidence for rs2583988. Large, multi-ethnic studies are warranted to elucidate underlying mechanisms and support precision medicine in PD.