Cord Blood DNA Methylation at CHD13 is Associated with Adiponectin Levels at 10-14 years of Age.

Background: Low adiponectin levels are associated with higher insulin resistance, development of type 2 diabetes, and greater adiposity in adults, but the evidence in youth is limited. This study aimed to assess adiponectin as a biomarker of adverse metabolic health in youth and to examine whether cord blood DNA methylation (cbDNAm) is associated with child adiponectin levels.

Methods: Participants from the Hyperglycemia and Adverse Pregnancy Outcome Study and Follow-up Study were included based on availability of cbDNAm, child anthropometry, child adiponectin levels, and glucose OGTT measures (N=2,265) collected at mean age 11.4 ± 1.2 years. Cross-sectional associations between child log-transformed adiponectin and child adiposity and glycemic measures were evaluated via partial correlation. Linear regression models were used for epigenome-wide analysis of cbDNAm and child adiponectin levels.

Results: After adjustment for co-variates, lower child adiponectin levels were correlated with higher adiposity/dysglycemia outcomes (sum of skinfolds, r= -0.285 and glucose sum of z-scores, r= -0.070) as well as lower Matsuda (r= 0.135) and disposition (r= 0.062) indices. Linear regression was used to assess associations between cbDNAm and child adiponectin levels with covariate adjustments. cbDNAm at cg02713721, located in the CDH13 locus, was associated with child adiponectin levels (β = 0.35, Bonferroni-adjusted p=0.01).

Conclusion: This study provides evidence of adiponectin as a biomarker of adverse metabolic health in youth. The association of methylation in CDH13, a gene involved in glucose regulation, with child adiponectin levels suggests a contribution to programming of future metabolic health.