Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation.
Journal: Molecular psychiatry
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Affiliated Institutions:
University of Cincinnati College of Medicine, Department of Environmental and Public Health Sciences, Cincinnati, OH, USA.
Erasmus MC, University Medical Center Rotterdam, Department of Adolescent and Child Psychiatry and Psychology, Rotterdam, Netherlands.
University of Michigan, School of Public Health, Department of Epidemiology, Ann Arbor, MI, USA.
Max Planck Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, Germany.
University of Cape Town, Department of Psychiatry and Mental Health, Cape Town, South Africa.
School of Psychology, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom.
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Helmholtz Centre for Environmental Research - UFZ, Department of Environmental Immunology, Leipzig, Germany.
Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, , NC, USA.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Department of Psychiatry and Mental Health, University of Cape Town, South Africa; and UCT Neuroscience Institute, Cape Town, South Africa.
Norwegian Institute of Public Health, Centre for Fertility and Health, Oslo, Norway.
University of Helsinki, Faculty of Medicine, Department of Psychology and Logopedics, Helsinki, Finland.
University of California-Davis, School of Medicine, Department of Public Health Sciences, Davis, CA, USA.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Department of Paediatrics & Child Health & SA-MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa.
University of Cincinnati College of Medicine, Department of Environmental and Public Health Sciences, Cincinnati, OH, USA. Kelly.Brunst@uc.edu.
Abstract summary
Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. This meta-analysis included twelve non-overlapping cohorts from ten independent longitudinal studies (N = 5,496) within the international Pregnancy and Childhood Epigenetics consortium to examine maternal stressful life events during pregnancy and DNA methylation in cord blood. Children whose mothers reported higher levels of cumulative maternal stressful life events during pregnancy exhibited differential methylation of cg26579032 in ALKBH3. Stressor-specific domains of conflict with family/friends, abuse (physical, sexual, and emotional), and death of a close friend/relative were also associated with differential methylation of CpGs in APTX, MyD88, and both UHRF1 and SDCCAG8, respectively; these genes are implicated in neurodegeneration, immune and cellular functions, regulation of global methylation levels, metabolism, and schizophrenia risk. Thus, differences in DNA methylation at these loci may provide novel insights into potential mechanisms of neurodevelopment in offspring.
Authors & Co-authors:
Kotsakis Ruehlmann Anna A
Sammallahti Sara S
Cortés Hidalgo Andrea P AP
Bakulski Kelly M KM
Binder Elisabeth B EB
Campbell Megan Loraine ML
Caramaschi Doretta D
Cecil Charlotte A M CAM
Colicino Elena E
Cruceanu Cristiana C
Czamara Darina D
Dieckmann Linda L
Dou John J
Felix Janine F JF
Frank Josef J
Håberg Siri E SE
Herberth Gunda G
Hoang Thanh T TT
Houtepen Lotte C LC
Hüls Anke A
Koen Nastassja N
London Stephanie J SJ
Magnus Maria C MC
Mancano Giulia G
Mulder Rosa H RH
Page Christian M CM
Räikkönen Katri K
Röder Stefan S
Schmidt Rebecca J RJ
Send Tabea S TS
Sharp Gemma G
Stein Dan J DJ
Streit Fabian F
Tuhkanen Johanna J
Witt Stephanie H SH
Zar Heather J HJ
Zenclussen Ana C AC
Zhang Yining Y
Zillich Lea L
Wright Rosalind R
Lahti Jari J
Brunst Kelly J KJ
Study Outcome
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