Sex-Specific Epigenetic Mediators Between Early Life Social Disadvantage and Adulthood BMI

Abstract

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.

Keywords::

• adipose tissue
• adiposity
• BMI
• childhood adversity
• DNA methylation
• epigenetics
• social disadvantage
• social epidemiology

Acknowledgements

The study protocol was approved by the institutional review boards at Brown University and Memorial Hospital of Rhode Island.

Financial & competing interests disclosure

This work was supported by the National Institute on Aging at the NIH (grant numbers RC2AG036666, R01AG048825), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Ministry of Science and Technology, Taiwan (grant number 105-2118-M-001-014-MY3). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the National Institute on Aging at the NIH (grant numbers RC2AG036666, R01AG048825), the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Ministry of Science and Technology, Taiwan (grant number 105-2118-M-001-014-MY3). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.