DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence. Issue 10 (2nd November 2018)

• Record Type: Journal Article
• Authors: Huang, Jian V.; Cardenas, Andres; Colicino, Elena; Schooling, C. Mary; Rifas-Shiman, Sheryl L.; Agha, Golareh; Zheng, Yinan; Hou, Lifang; Just, Allan C.; Litonjua, Augusto A.; DeMeo, Dawn L.; Lin, Xihong; Oken, Emily; Hivert, Marie-France; Baccarelli, Andrea A.
• Is Part Of: Epigenetics. Volume 13:Issue 10/11(2018)
• Page Start: 1072
• Page End: 1087
• Publication Date: 2018-11-02
• Subjects: Obesity -- BMI -- cardio-metabolic -- DNA methylation -- epigenetics -- mediation; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2018.1543503
• Languages: English
• ISSNs: 1559-2294

Abstract

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.