Epigenome-wide association study of peripheral immune cell populations in Parkinson’s disease

Abstract

Understanding the contribution of immune mechanisms to Parkinson’s disease pathogenesis is an important challenge, potentially of major therapeutic implications. To further elucidate the involvement of peripheral immune cells, we studied epigenome-wide DNA methylation in isolated populations of CD14+ monocytes, CD19+ B cells, CD4+ T cells, and CD8+ T cells from Parkinson’s disease patients and healthy control participants. We included 25 patients with a maximum five years of disease duration and 25 controls, and isolated four immune cell populations from each fresh blood sample. Epigenome-wide DNA methylation profiles were generated from 186 samples using the Illumina MethylationEpic array and association with disease status was tested using linear regression models. We identified six differentially methylated CpGs in CD14+ monocytes and one in CD8 + T cells. Four differentially methylated regions were identified in monocytes, including a region upstream of RAB32, a gene that has been linked to LRRK2. Methylation upstream of RAB32 correlated negatively with mRNA expression, and RAB32 expression was upregulated in Parkinson’s disease both in our samples and in summary statistics from a previous study. Our epigenome-wide association study of early Parkinson’s disease provides evidence for methylation changes across different peripheral immune cell types, highlighting monocytes and the RAB32 locus. The findings were predominantly cell-type-specific, demonstrating the value of isolating purified cell populations for genomic studies.

Epigenome-wide association study, meta-analysis and risk profiling of whole blood in Parkinson’s disease

“…The PD and control participants in the Oslo cohort were recruited from 2007-2020 at the Department of Neurology, Oslo University Hospital, Norway (47,48). All PD patients underwent neurological examination and were diagnosed based on the UK Parkinson's Disease Society Brain Bank criteria (49), with the exception that more than one affected relative was not regarded an exclusion criterion.…”