Lack of association between G6PD variants and Parkinson’s disease

Oxidative stress has been implicated in Parkinson’s disease (PD). Genes involved in PD, such as PRKN, PINK1 and PARK7 , contribute to oxidative stress in dopaminergic neurons. The X-linked G6PD gene encodes glucose 6-phosphate dehydrogenase, an important regulator of oxidative stress. Recent studies suggested that alpha-synuclein aggregates may impair G6PD activity and contribute to dopaminergic neuron loss, and that G6PD mutations may independently increase the risk of PD. In this study, we aimed to examine the role of common and rare G6PD variants in PD across six cohorts including 8,905 PD patients, 16,770 proxy-patients, 394,098 controls. These cohorts were analyzed after stratification by sex and then combined to account for the G6PD X-linked location. Using logistic regression, we did not identify significant associations for common variants in any of the cohorts. The Combined and Multivariate Collapsing Wald (CMC-Wald) test was performed to assess the cumulative effect of rare variants (minor allele frequency < 0.01) across six cohorts, followed by a meta-analysis, also demonstrating lack of association. In conclusion, we did not find evidence for a role for G6PD in PD.