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Variation in DNA methylation of the oxytocin receptor gene predicts children's resilience to prenatal stress

  • Izabela Milaniak (a1), Charlotte A. M. Cecil (a2), Edward D. Barker (a2), Caroline L. Relton (a3), Tom R. Gaunt (a3), Wendy McArdle (a3) and Sara R. Jaffee (a1)...

Abstract

Emerging research in epigenetics has shown that there is variability in how environmental exposures “get under the skin” through mechanisms like DNA methylation to influence gene expression that may lead to differential adaptations to stress. This is the first study to examine prospectively the relationship between DNA methylation at birth and resilience to prenatal environmental stressors in several domains (conduct, hyperactivity, emotional problems, and global symptomatology) in middle childhood. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously associated with impairments in social–cognitive processes that may underlie a wide range of childhood psychopathology. Participants were 91 youth exposed to pre- and postnatal adversity with established conduct problem trajectories drawn from the Avon Longitudinal Study of Parents and Children. Consistent with our hypothesis, OXTR DNA methylation was predictive of resilience in the conduct problems domain in middle childhood. DNA methylation profiles did not predict resilience in domains of emotional, hyperactivity, and global symptomatology, suggesting a potential role for OXTR in the development of conduct problems in particular. However, individuals who were resilient to conduct problems were also broadly resilient across multiple domains. Therefore, future research should elucidate the biological pathways between OXTR DNA methylation and gene expression and its relation to impairments in social behavior.

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Corresponding author

Address correspondence and reprint requests to: Sara Jaffee, Department of Psychology, University of Pennsylvania, 425 South University Avenue, Philadelphia, PA 19104; E-mail: srjaffee@psych.upenn.edu.

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We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole Avon Longitudinal Study of Parents and Children (ALSPAC) team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. With regard to the ALSPAC DNA methylation, we thank all involved, particularly the laboratory scientists and bioinformaticians who contributed considerable time and expertise to the data in this paper. The UK Medical Research Council and the Wellcome Trust (Grant 102215/2/13/2) and the University of Bristol provide core support for the ALSPAC. This publication is the work of the authors, who will serve as guarantors for the contents of this paper. This research was specifically supported by National Institute of Child and Human Development Grant R01HD068437 (to E.D.B.). ARIES was funded by the BBSRC (Grants BBI025751/1 and BB/I025263/1). Funding was provided by the Medical Research Council Integrative Epidemiology Unit at the University of Bristol Grants MC_UU_12013/2 and MC_UU_12013/8 (to C.L.R. and T.R.G). Finally, support was provided by the Economic and Social Research Council Grant ES/N001273/1 (to C.A.M.C.).

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