Parkinson's Disease-Associated, Sex-specific Changes in DNA Methylation at PARK7 (DJ-1), ATXN1, SLC17A6, NR4A2, and PTPRN2 in Cortical Neurons

• Published in: bioRxiv
• Main Authors: Kochmanski, Joseph, Kuhn, Nathan C, Bernstein, Alison I
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 09.09.2021; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Aging; Cortex (parietal); Deoxyribonucleic acid; DNA; DNA methylation; Environmental factors; Epigenetics; Genomes; Movement disorders; Neurodegenerative diseases; Neuroscience; Nuclear receptors; Nurr1 protein; PARK7 protein; Parkinson's disease; Parkinsons disease; Sex differences
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2021.09.08.459434

Evidence for epigenetic regulation playing a role in Parkinson's disease (PD) is growing, particularly for DNA modifications. Approximately 90% of PD cases are due to a complex interaction between age, genes, and environmental factors, and epigenetic marks are thought to mediate the relationship between aging, genetics, the environment, and disease risk. To date, there are a small number of published genome-wide studies of DNA modifications in PD, but none accounted for cell-type or sex in their analyses. Given the hetereogeneity of bulk brain tissue samples and known sex differences in PD risk, progression, and severity, these are critical variables to account for. In this first genome-wide analysis of DNA methylation in an enriched neuronal population from PD post-mortem parietal cortex, we report sex-specific PD-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance. Competing Interest Statement The authors have declared no competing interest.