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

3 Citations (Scopus)

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

Fingerprint

DNA Methylation
Body Mass Index
Epigenomics
Sample Size
Leukocytes
Obesity

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., ... 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
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. / DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence. In: Epigenetics. 2018 ; Vol. 13, No. 10-11. pp. 1072-1087.
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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.",
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Huang, JV, Cardenas, A, Colicino, E, Schooling, CM, Rifas-Shiman, SL, Agha, G, Zheng, Y, Hou, L, Just, AC, Litonjua, AA, DeMeo, DL, Lin, X, Oken, E, Hivert, MF & Baccarelli, AA 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, vol. 13, no. 10-11, pp. 1072-1087. https://doi.org/10.1080/15592294.2018.1543503

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

In: Epigenetics, Vol. 13, No. 10-11, 02.11.2018, p. 1072-1087.

Research output: Contribution to journalArticle

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AU - Huang, Jian V.

AU - Cardenas, Andres

AU - Colicino, Elena

AU - Schooling, C. Mary

AU - Rifas-Shiman, Sheryl L.

AU - Agha, Golareh

AU - Zheng, Yinan

AU - Hou, Lifang

AU - Just, Allan C.

AU - Litonjua, Augusto A.

AU - DeMeo, Dawn L.

AU - Lin, Xihong

AU - Oken, Emily

AU - Hivert, Marie France

AU - Baccarelli, Andrea A.

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N2 - 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.

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KW - epigenetics

KW - mediation

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