DNA Methylation Age Acceleration as a Potential Biomarker for Early Onset of Rapid Eye Movement Sleep Behavior Disorder

Abstract

REM sleep behavior disorder (RBD) is the strongest prodromal marker for α‐synucleinopathies. The Horvath DNA‐methylation‐age (DNAm‐age) is an epigenetic clock reflecting biological aging. We found an association of DNAm‐age‐acceleration with RBD age‐at‐onset at baseline (N=162; B=‐0.68; SE=0.12; P=2.59e‐08) and follow‐up (N=45; B=‐1.07; SE=0.21; P=9.73e‐06). The result remains similar after accounting for genetic risk‐factors (e.g., RBD polygenic risk score). On average, RBD patients with faster vs slow/normal epigenetic aging had a 5.2‐year earlier phenoconversion, and the cox‐regression analysis revealed a trend towards significance (N=53; HR=1.05 (0.99–1.11); P=0.06). Our findings suggest that DNAm‐age‐acceleration is a potential biomarker for earlier RBD onset.This article is protected by copyright. All rights reserved.