Findings from our study converge to several lines of evidence, namely the concordant meQTL/eQTL effect in the CNS, methylation-mediated CHD1L regulation, and detection of dysregulated CHD1L-gene network pertaining to neuronal processes in the PPMS brain, implicating CHD1L in neuronal vulnerability in PPMS. Here, CHD1L is linked to primary progressive multiple sclerosis.