Cross‐Tissue Specificity of Pediatric DNA Methylation Associated With Cumulative Family Stress

Cumulative family stress (cumulative FS), characterized by mother-reported co-occurring stressors in a family context, may be biologically embedded through DNA methylation (DNAm) and contribute to later health outcomes, including psychopathology. To illuminate tissue specificity in association with cumulative FS across two accessible tissues, we compared epigenome-wide DNAm associations in buccal epithelial cells (BECs; n = 218) and peripheral blood mononuclear cells (PBMCs; n = 51) from 7- to 13-year-old children in Canada, accounting for sex, age, predicted cell-type proportion, and genetic ancestry. We found that higher levels of cumulative FS were associated with DNAm at seven sites, primarily in stress- and immune-related genes, only in PBMCs but not in BECs. Matched tissue samples (n = 50) also indicated limited cross-tissue concordance. These associations were partly explained by negative but not positive mother-child relationship. Our findings suggested that PBMC DNAm can be used as a marker for biological embedding of cumulative FS and highlighted cross-tissue specificity of the associations of DNAm with cumulative FS.