Meta-analysis of DNM1L variants in Parkinson's Disease

To confirm the involvement of DNM1L variants in PD susceptibility, a meta-analysis combining public studies and our case–control study was conducted. In addition to our data, summary data from the PD variant browser were included in the meta-analysis, which comprised four studies: PD Genome Project, International Parkinson's Disease Genomic Consortium (IPDGC) Exomes, IPDGC Resequencing Project, and UK Biobank (19 (link)). Unlike our cohorts, these cohorts mainly contain European populations, which can increase the power to detect the association between DNM1L variants and PD. As no rare variants of DNM1L found in our cohort were seen in included public data, we only validated the significant association between significant common variants of DNM1L and PD in meta-analysis. We used the Hardy-Weinberg equilibrium model to estimate the SNPs in all cohorts and then excluded the variants with deviations in controls (p < 0.05). To assess the strength of the association between DNM1L variants and PD risk, a pooled OR and 95% confidence intervals (CIs) were calculated under five different models (allele, dominant, recessive, heterozygote, and homozygote model). The Cochrane Q-test and I² statistics were used to assess study heterogeneity and a significant Q-test (p < 0.1 or I² > 50%) indicated heterogeneity. Fixed- or random-effects models were selected based on the presence or absence of heterogeneity. A Z-test determined the significance of the pooled ORs. We used the FDR method to correct p-values for multiple comparisons for the variant association analysis. A p-value of < 0.05 was considered statistically significant. Moreover, the p-values of Egger's and Begg's tests were calculated to estimate the publication bias. All analyses were performed using the R package “meta.”