INTRODUCTION: Alcohol consumption can induce a neuroinflammatory response and contribute to the progression of neurodegeneration. However, its association with Parkinson's disease (PD), the second most common neurodegenerative disorder, remains undetermined. Recent studies suggest that the glycoprotein non-metastatic melanoma protein B (GPNMB) is a potential biomarker for PD. We evaluated the association of rs199347, a variant of the gene, with alcohol consumption and methylation upstream of . METHODS: We retrieved genetic and DNA methylation data obtained from participants enrolled in the Taiwan Biobank (TWB) between 2008 and 2016. After excluding individuals with incomplete or missing information about potential PD risk factors, we included 1,357 participants in our final analyses. We used multiple linear regression to assess the association of rs199347 and chronic alcohol consumption (and other potential risk factors) with cg17274742 methylation. RESULTS: There was no difference between the distribution of rs199347 genotypes between chronic alcohol consumers and the other study participants. A significant interaction was observed between the GPNMB variant and alcohol consumption (p = 0.0102) concerning cg17274742 methylation. Compared to non-chronic alcohol consumers with the AA genotype, alcohol drinkers with the rs199347 GG genotype had significantly lower levels (hypomethylation) of cg17274742 (p = 0.0187). CONCLUSION: Alcohol consumption among individuals with the rs199347 GG genotype was associated with lower levels of cg17274742 methylation, which could increase expression of the gene, an important neuroinflammatory-related risk gene for PD.