Research Paper Volume 8, Issue 7 pp 1485—1512

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

class="figure-viewer-img"

Figure 1. Epigenetic clock analysis of non-cerebellar brain regions. (A) Scatter plot of (winsorized) DNAm age versus chronological age (x-axis). Red dots correspond to HD cases, black dots to non-HD samples. The curve corresponds to a spline regression line (2 degrees of freedom) through the non-HD samples. Epigenetic age acceleration was defined as the vertical distance of each sample from the spline regression line. (B) HD Vonsattel grade vs the proportion of neurons (y-axis). The proportion of neurons was estimated based on DNA methylation data using the CETS method [23]. (C,D) HD status versus (C) epigenetic age acceleration, D) an intrinsic measure of epigenetic age acceleration that adjusts for the proportion of neurons. (E,F) HD Vonsattel grade versus (E) age acceleration and (F) an intrinsic measure of epigenetic age acceleration that adjusts for the proportion of neurons. All bar plots show the mean value (y-axis) and one standard error and report the results from a non-parametric group comparison test (Kruskal Wallis). The “winsorized” the DNAm age estimates changed the values of four putative outliers as described in Supplementary Figure 1.