Joan Kaufman1, Janitza L Montalvo-Ortiz2, Hannah Holbrook3, Kerry O'Loughlin3, Catherine Orr3, Catherine Kearney4, Bao-Zhu Yang2, Tao Wang5, Hongyu Zhao6, Robert Althoff3, Hugh Garavan3, Joel Gelernter7, James Hudziak3. 1. Center for Child and Family Traumatic Stress, Kennedy Krieger Institute, Baltimore, MD; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD; Department of Psychiatry, Yale University, New Haven, CT. Electronic address: joan.kaufman@kennedykrieger.org. 2. Department of Psychiatry, Yale University, New Haven, CT. 3. Vermont Center for Children, Youth, and Families, Department of Psychiatry, University of Vermont, Burlington, VT. 4. Center for Child and Family Traumatic Stress, Kennedy Krieger Institute, Baltimore, MD. 5. Department of Biostatistics, Yale University, New Haven, CT; Department of Bioinformatics and Biostatistics, Shanghai Jiao Tong University, Shanghai, China. 6. Department of Biostatistics, Yale University, New Haven, CT. 7. Department of Psychiatry, Yale University, New Haven, CT; Veterans Administration, West Haven, CT.
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.
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.
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Authors: Nicholas F Wymbs; Catherine Orr; Matthew D Albaugh; Robert R Althoff; Kerry O'Loughlin; Hannah Holbrook; Hugh Garavan; Janitza L Montalvo-Ortiz; Stewart Mostofsky; James Hudziak; Joan Kaufman Journal: Child Abuse Negl Date: 2020-02-14
Authors: Bradley R Grant; Kerry O'Loughlin; Hannah M Holbrook; Robert R Althoff; Catherine Kearney; Francheska Perepletchikova; Damion J Grasso; James J Hudziak; Joan Kaufman Journal: Int Rev Psychiatry Date: 2019-12-27