Lack of association between G6PD variants and Parkinson disease

Oxidative stress has been implicated in Parkinson 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 6 cohorts, including 8,905 PD cases, 16,770 proxy cases, and 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 optimized sequence Kernel association (SKAT-O) test was performed to assess the effect of rare variants (minor allele frequency <0.01) across six cohorts, followed by a meta-analysis using metaSKAT, also demonstrating lack of association. In conclusion, we did not find evidence for a role for G6PD in PD.