Extended Data Fig. 4: Independent validation of DNA methylation changes at enhancers, genome-wide, in PD neurons.

Differential methylation at enhancers in PD prefrontal cortex neurons identified in the discovery cohort were validated with an independent replication cohort of prefrontal cortex neurons from 27 PD patients and 31 controls. a, Manhattan plot showing differentially methylated cytosines at enhancers in PD neurons, identified by logistic regression after adjusting for age, sex, postmortem interval, and neuronal subtypes. -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). b, Proportion of hypermethylated (red) and hypomethylated (blue) cytosines at enhancers in PD replication cohort. Enrichment determined by Fisher’s exact test with OR referring to the odds ratio and P = 10⁻⁶ is the significance of hypermethylation enrichment. Gray is all cytosines in the analysis (background). c, Correlation between the discovery and replication cohort in the DNA methylation fold changes at enhancer cytosine sites in PD neurons. P = 10⁻¹¹¹ is the significance of Pearson’s correlation by two-tailed t-test. d, Intersection of the genes with differentially methylated cytosines at their enhancers in the discovery and replication cohort. P = 10⁻⁷⁹ is the significance of overlap determined by Fisher’s exact test.