Our analyses of multiple brain regions with different degrees of GCI pathology, demonstrated that some DNA methylation changes mirror the MSA-associated pathology (i.e. cerebellum-specific or at least stronger effects in the cerebellum, the most severely affected brain region analysed), such as CpGs in SRP9 and DGKI. We also detected changes shared with other neurodegenerative diseases, including changes in HIP1, LMAN2, MOBP and in the HOXA gene cluster, suggesting these loci could be involved in common mechanisms implicated in neurodegeneration. Here, MOBP is linked to multiple system atrophy.