Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth - PubMed (original) (raw)

. 2018 Nov:202:150-156.e3.

doi: 10.1016/j.jpeds.2018.06.051. Epub 2018 Aug 31.

Janitza L Montalvo-Ortiz 2, Hannah Holbrook 3, Kerry O'Loughlin 3, Catherine Orr 3, Catherine Kearney 4, Bao-Zhu Yang 2, Tao Wang 5, Hongyu Zhao 6, Robert Althoff 3, Hugh Garavan 3, Joel Gelernter 7, James Hudziak 3

Affiliations

Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth

Joan Kaufman et al. J Pediatr. 2018 Nov.

Abstract

Objective: To determine if measures of adverse childhood experiences and DNA methylation relate to indices of obesity in youth.

Study design: Participants were derived from a cohort of 321 8 to 15-year-old children recruited for an investigation examining risk and resilience and psychiatric outcomes in maltreated children. Assessments of obesity were collected as an add-on for a subset of 234 participants (56% female; 52% maltreated). Illumina arrays were used to examine whole genome epigenetic predictors of obesity in saliva DNA. For analytic purposes, the cohort analyzed in the first batch comprised the discovery sample (n = 160), and the cohort analyzed in the second batch the replication sample (n = 74).

Results: After controlling for race, sex, age, cell heterogeneity, 3 principal components, and whole genome testing, 10 methylation sites were found to interact with adverse childhood experiences to predict cross-sectional measures of body mass index, and an additional 6 sites were found to exert a main effect in predicting body mass index (P < 5.0 × 10-7, all comparisons). Eight of the methylation sites were in genes previously associated with obesity risk (eg, PCK2, CxCl10, BCAT1, HID1, PRDM16, MADD, PXDN, GALE), with several of the findings from the discovery data set replicated in the second cohort.

Conclusions: This study lays the groundwork for future longitudinal studies to elucidate these mechanisms further and identify novel interventions to alleviate the health burdens associated with early adversity.

Keywords: ACE; DNA methylation; child abuse; obesity.

Copyright © 2018 Elsevier Inc. All rights reserved.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1

Figure 1

Quantile-quantile (Q-Q) plots. The figure above depicts the Q-Q plots for the P values of the association. The genomic inflation factor for the discovery cohort was 1.004, indicating that the epigenome wide analyses results are negligibly inflated and the results are unlikely due to spurious findings.

Figure 2

Figure 2

Indirect effects of intrafamilial childhood adversities on BMI through methylation of PCK2. After controlling for the relevant demographic factors (eg, age, sex, race), cell heterogeneity measures (eg, CD34, CD14, and buccal cells), and the first 3 PCs, support for a mediation model was attained, with the effects of intrafamilial childhood adversities on indices of obesity found to be mediated by epigenetic changes in the PCK2, a gene implicated in obesity risk in a prior epigenome wide study.

References

    1. CDC. Adverse childhood experiences reported by adults—five states, 2009. MMWR Morb Mortal Wkly Rep 2010;59:1609–13. Reprinted in JAMA, 2011; 305(7):666–669. - PubMed
    1. Kuehn BM. AAP: toxic stress threatens kids’ long-term health. JAMA 2014;312:585–6. doi: 10.1001/jama.2014.8737. - DOI - PubMed
    1. Shonkoff JP, Boyce WT, McEwen BS. Neuroscience, molecular biology, and the childhood roots of health disparities: building a new framework for health promotion and disease prevention. JAMA 2009;301:2252–9. - PubMed
    1. Anda RF, Croft JB, Felitti VJ, Nordenberg D, Giles WH, Williamson DF, et al. Adverse childhood experiences and smoking during adolescence and adulthood. JAMA 1999;282:1652–8. - PubMed
    1. Kendler KS, Bulik CM, Silberg J, Hettema JM, Myers J, Prescott CA. Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry 2000;57:953–9. - PubMed

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