The Million Veteran Program (MVP) data set will be used to identify new genetic risk variants— including copy number variants (CNVs: deletions and duplications in the genome)—for Parkinson disease (PD). Previously identified genetic risk factors will be better characterized by testing all pairwise gene-by-gene interactions and testing if variants associated with mRNA expression levels are predictive of PD risk using PrediXcan. The MVP intake questionnaire captured previously identified environmental risk factors such as head trauma (traumatic brain injury) and pesticide exposure; these will be accounted for in the study through gene-by- environment tests to determine if the effects of variants are mediated by these exposures. This will also be the first GWAS of PD to analyse significant Hispanic and African American populations, which will reveal if the variants identified using individuals of European descent are generalizable to other populations. In addition, replication of an association between lower mitochondrial DNA copy number (mtDNA CN) in the blood and PD will be attempted, possibly establishing mtDNA CN as a biomarker for PD risk and progression, which could later be used in clinical trials or even in the clinic. mtDNA CN will be measured using a novel approach that we developed to determine the relative signal intensity for mitochondrial probes on a GWAS array compared to the corresponding signal intensity for nuclear probes. Mendelian randomization experiments would then be employed to see if there is evidence that low mtDNA CN causes PD or whether the PD pathology causes the mtDNA CN to decrease. These experiments will reveal new information regarding the biology of Parkinson disease, allow for better risk stratification, and potentially reveal targets for novel therapeutics.