DNA methylation-based surrogates of plasma proteins are associated with Parkinson's disease risk.

BACKGROUND:The epigenome may reflect Parkinson's disease (PD) risk, which serves as a point of convergence of genetic and environmental risk factors. Here, we investigate whether blood DNA methylation (DNAm) markers are associated with PD risk. METHODS:We selected 12 plasma proteins known as predictors of cardiovascular conditions and mortality to evaluate their effects on PD risk in a case-control study. In lieu of protein level measures, however, we assessed the influence of their DNAm surrogates. Primary analysis was restricted to 569 PD patients and 238 controls with DNAm data available. Using univariate logistic regression, we evaluated associations between the DNAm markers and PD. RESULTS:Of the 12 DNAm surrogates, the most robustly associated were DNAm EFEMP-1 and DNAm CD56, which were associated with PD with and without controlling for blood cell composition. DNAm EFEMP-1 was associated with a decreased risk of PD (OR = 0.83 per SD, 95% CI = 0.70, 0.98) whereas DNAm CD56 was associated with an increased risk of PD (OR = 1.41, 95% CI = 1.11, 1.79). CONCLUSIONS:Several DNAm markers, selected as part of a panel to track cardiovascular outcomes and mortality, were associated with PD risk. DNAm markers may inform of factors that are affected differentially in early PD patients compared with controls.