Sex-specific epigenetic mediators between early life social disadvantage and adulthood BMI

Aim: The objective of this study was to identify potential epigenetic mediating pathways linking early life social disadvantage (ELSD) to adulthood BMI. Methods: Sex-specific epigenome-wide two-stage mediation analyses were conducted in blood and adipose tissue, and mediation estimates were obtained using cross-product mediation analysis. Pathway analyses were conducted using GREAT software (Bejerano Lab, CA, USA). Results: Candidate mediation CpG sites were identified in adipose tissue, but not blood, and were sex-specific. Significant mediation sites in females included CpG loci in genes: PKHG1, BCAR3, ADAM5P, PIEZO1, FGFRL1, FASN and DPP9, among others. Pathway analyses revealed evidence of enrichment for processes associated with TFG-β signaling and immunologic signatures. In males, significant mediation loci included sites in MAP3K5 and RPTOR, which have previously been associated with adipogenesis, inflammation and insulin resistance. Conclusion: Our findings provide supportive evidence for the mediating role of epigenetic mechanisms in the effect of early life social disadvantage on adulthood BMI.