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

An increasing body of evidence indicates altered DNA methylation in Parkinson’s disease (PD), yet the reproducibility and utility of such methylation changes are largely unexplored. We conducted an epigenome-wide association study (EWAS) in whole blood, including 280 PD and 279 control participants from Oslo, Norway. In meta-analysis with data from the Parkinson’s Progression Markers Initiative (PPMI) and a previously published whole blood PD EWAS (total N=3068) we confirm SLC7A11 hypermethylation and nominate a novel suggestive differentially methylated CpG near LPIN1 . A joint multiscore risk profiling model incorporating polygenic risk and methylation-based estimates of epigenetic PD risk, smoking and leukocyte proportions differentiated patients from control participants with an area under the receiver-operator curve or 0.82 in the Oslo cohort and 0.65 in PPMI. Our results highlight the power of DNA methylation profiling to capture multiple aspects of disease risk, indicating a biomarker potential for precision medicine in neurodegenerative disorders.