Genome-Wide DNA Methylation Profiling of Peripheral Blood Mononuclear Cells Reveals Epigenetic Signatures in Autism Spectrum Disorder.

Furthermore, overlapping with the age-stratified cohort (Corley et al., 2019), our PBMC signatures aligned strongly with the post mortem brain of the young cohort, such as in all ASD with 25 overlaps at a 76% consistency rate (hypergeometric p -value = 4.45 × 10 −15 , adjusted p -value = 5.34 × 10 −14 ), however, directional consistency across these age-stratified groups did not reach statistical significance (binomial p -value = 0.015 and adjusted p -value = 0.050) [ 28 ].

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To minimize bias and provide a biological context, we focused on both the top nominally significant functions and functions previously implicated in ASD, as shown in Table 3 .

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We found highly significant enrichment of DMP genes among all SFARI gene categories across all phenotypic groups, with the most robust enrichment observed in the moderate ASD group (87 overlapping genes, adjusted p -value < 0.001), followed by severe ASD (62 genes, adjusted p -value = 0.001) and all ASD (62 genes, adjusted p -value = 0.001) ( Table 4 and Figure 5 A–C).

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