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Fig. 4 | Epigenetics & Chromatin

Fig. 4

From: DNA methylation analysis on purified neurons and glia dissects age and Alzheimer’s disease-specific changes in the human cortex

Fig. 4

Meta-analysis and integration of external brain tissue data. a Manhattan plot for the Braak stage meta-analysis. Selected CpGs located at the genes LRRC8B, HOXA3 and APP are marked by arrows. b Cluster analysis for the 200 top-ranking Braak-DMCGs. c Methylation change over Braak stages for exemplary top CpGs at the genes HOX3A (top), LRRC8B (middle) and APP (bottom). Box colored as in b. d Methylation change between Braak stages for various CpG sets based on our own data (Study 1: our sorted and tissue samples) or on external tissue data (Study 2: GSE59685 [82]; Study 3: GSE80970 [121]). Rows are organized as sets of CpGs derived from our own 200 top-ranking results (neuron, glia, meta-analysis), the top 100’s from Lunnon and partners (FC, TC, EC, CER) and 100 randomly selected sites. Dashed squares indicate the dataset initially used to identify the corresponding CpG set. ‘Cross study’ depicts two CpGs at the HOXA3 locus co-identified in our screen and in Study 2. Note that for most CpGs the methylation difference across Braak stages are strongest in sorted samples even when the CpG set was originally identified in tissues. (FC: frontal cortex, TC: temporal cortex, EC: entorhinal cortex) (color figure online)

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