Su H Chu1,2, Eric B Loucks1, Karl T Kelsey1,3, Stephen E Gilman4,5,6,7, Golareh Agha8, Charles B Eaton1,9, Stephen L Buka1, Yen-Tsung Huang1,10,11. 1. Department of Epidemiology, Brown School of Public Health, Providence, RI, 02912, USA. 2. Channing Division of Network Medicine, Brigham & Women's Hospital & Harvard Medical School, Boston, MA, 02115, USA. 3. Department of Pathology & Laboratory Medicine, Brown University Warren Alpert Medical School, Providence, RI, 02912, USA. 4. Health Behavior Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, Bethesda, MD, 20892, USA. 5. Department of Social & Behavioral Sciences, Harvard TH Chan School of Public Health, Boston, MA, 02115, USA. 6. Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, 02115, USA. 7. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. 8. Columbia Aging Center, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA. 9. Department of Family Medicine, Brown University Warren Alpert Medical School, Providence, RI, 02912, USA. 10. Department of Biostatistics, Brown School of Public Health, Providence, RI, 02912, USA. 11. Institute of Statistical Science, Academia Sinica, Taipei, 11529, Taiwan.
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.
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.
Entities:
Keywords:
BMI; DNA methylation; adipose tissue; adiposity; childhood adversity; epigenetics; social disadvantage; social epidemiology
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