Extended Data Fig. 3: Epigenetic changes in the prefrontal cortex precede the arrival of PD pathology.
From: Epigenomic analysis of Parkinson’s disease neurons identifies Tet2 loss as neuroprotective
Differentially methylated cytosines in neurons of the PD prefrontal cortex before the arrival of Lewy pathology (PD Braak stage 3–4, n = 22 individuals, green), after the arrival of Lewy pathology (PD Braak stage 5–6, n = 34 individuals, yellow) and in the combined PD group (n = 57 individuals, red), in comparison to healthy controls (n = 48 individuals). a, b, Manhattan plot showing differentially methylated cytosines in PD neurons before (a) and after (b) the arrival of Lewy pathology. -log10(PValue) refers to the significance of cytosine methylation change in PD, with the sign corresponding to the direction of change (red: hypermethylated, blue: hypomethylated cytosine in PD). Threshold for genome-wide significance is q < 0.05 (black line, multiple testing corrected). c, Density plot of differentially methylated cytosines in PD prefrontal cortex neurons before and after arrival of Lewy pathology. Enrichment determined by Fisher’s exact test with OR referring to the odds ratio and p-value is significance of hypermethylation enrichment. d, Intersection of differentially methylated cytosines in PD prefrontal cortex neurons in the combined PD group and before or after arrival of Lewy pathology.
