Parkinson’s disease-associated, sex-specific changes in DNA methylation at PARK7 (DJ-1), ATXN1, SLC17A6, NR4A2, and PTPRN2 in cortical neurons

Evidence for epigenetic regulation playing a role in Parkinson’s disease
(PD) is growing, particularly for DNA methylation. 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
methylation in PD, but none accounted for cell-type or sex in their
analyses. Given the heterogeneity 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.