DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence

Jian V. Huang*, Andres Cardenas, Elena Colicino, C. Mary Schooling, Sheryl L. Rifas-Shiman, Golareh Agha, Yinan Zheng, Lifang Hou, Allan C. Just, Augusto A. Litonjua, Dawn L. DeMeo, Xihong Lin, Emily Oken, Marie France Hivert, Andrea A. Baccarelli

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Obesity is associated with higher cardio-metabolic risk even in childhood and adolescence; whether this association is mediated by epigenetic mechanisms remains unclear. We examined the extent to which mid-childhood body mass index (BMI) z-score (median age 7.7 years) was associated with cardio-metabolic risk score in early adolescence (median age 12.9 years) via mid-childhood DNA methylation among 265 children in the Project Viva. We measured DNA methylation in leukocytes using the Infinium Human Methylation450K BeadChip. We assessed mediation CpG-by-CpG using epigenome-wide association analyses, high-dimensional mediation analysis, and natural effect models. We observed mediation by mid-childhood DNA methylation at 6 CpGs for the association between mid-childhood BMI z-score and cardio-metabolic risk score in early adolescence in the high-dimensional mediation analysis (accounting for 10% of the total effect) and in the natural effect model (β = 0.04, P = 3.2e-2, accounting for 13% of the total effect). The natural direct effect of BMI z-score on cardio-metabolic risk score was still evident (β = 0.27, P = 1.1e-25). We also observed mediation by mid-childhood DNA methylation at 5 CpGs that was in the opposite direction from the total effect (natural effect model: β = −0.04, P = 2.0e-2). Mediation in different directions implies a complex role of DNA methylation in the association between BMI and cardio-metabolic risk and needs further investigation. Future studies with larger sample size and greater variability in cardio-metabolic risk will further help elucidate the role of DNA methylation for cardio-metabolic risk.

Original languageEnglish (US)
Pages (from-to)1072-1087
Number of pages16
JournalEpigenetics
Volume13
Issue number10-11
DOIs
StatePublished - Nov 2 2018

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Keywords

  • BMI
  • DNA methylation
  • Obesity
  • cardio-metabolic
  • epigenetics
  • mediation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Huang, J. V., Cardenas, A., Colicino, E., Schooling, C. M., Rifas-Shiman, S. L., Agha, G., Zheng, Y., Hou, L., Just, A. C., Litonjua, A. A., DeMeo, D. L., Lin, X., Oken, E., Hivert, M. F., & Baccarelli, A. A. (2018). DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence. Epigenetics, 13(10-11), 1072-1087. https://doi.org/10.1080/15592294.2018.1543503