Department of Economics and Business Economics

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Darina Czamara, Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany.
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  • Gökçen Eraslan, School of Life Sciences, Weihenstephan, Technische Universität München, Freising, 85354, Germany.
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  • Christian M Page, Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, 0213, Norway.
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  • Jari Lahti, Helsinki Collegium for Advanced Studies, University of Helsinki, Helsinki, 00101, Finland.
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  • Marius Lahti-Pulkkinen, British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
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  • Esa Hämäläinen, HUSLAB and Department of Clinical Chemistry, Helsinki University, Helsinki, 00290, Finland.
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  • Eero Kajantie, National Institute for Health and Welfare, Children's Hospital, Helsinki University Hospital, 00271, Helsinki, Finland.
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  • Hannele Laivuori, Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, 33100, Finland.
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  • Pia M Villa, Medical and Clinical Genetics and Obstetrics and Gynaecology University of Helsinki and Helsinki University Central Hospital, Helsinki, 00014, Finland.
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  • Rebecca M Reynolds, British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
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  • Wenche Nystad, Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, 0213, Norway.
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  • Siri E Håberg, Center for Fertility and Health, Norwegian Institute of Public Health, Oslo, 0213, Norway.
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  • Stephanie J London, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, North Carolina, 20814, USA.
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  • Kieran J O'Donnell, Sackler Program for Epigenetics and Psychobiology at McGill University, Montreal, H3A 0G4, QC, Canada.
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  • Elika Garg, Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, H3A 2B4, QC, Canada.
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  • Michael J Meaney, Singapore Institute for Clinical Sciences, Singapore, 117609, Singapore.
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  • Sonja Entringer, University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, 92697, USA.
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  • Pathik D Wadhwa, Department of Psychiatry and Human Behavior, Obstetrics and Gynecology, and Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, 92697, USA.
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  • Claudia Buss, University of California, Irvine, Development, Health, and Disease Research Program, Orange, CA, 92697, USA.
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  • Meaghan J Jones, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
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  • David T S Lin, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
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  • Julie L MacIsaac, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
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  • Michael S Kobor, Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia and the BC Children's Hospital Research Institute, Vancouver, V5Z 4H4, BC, Canada.
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  • Nastassja Koen, South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, Cape Town, 7505, South Africa.
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  • Heather J Zar, Department of Paediatrics & Child Health and SAMRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, 7505, South Africa.
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  • Karestan C Koenen, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
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  • Shareefa Dalvie, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, 7925, South Africa.
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  • Dan J Stein, South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, Cape Town, 7505, South Africa.
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  • Ivan Kondofersky, Department of Mathematics, Technische Universität München, Munich, 85748, Germany.
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  • Nikola S Müller, Institute of Computational Biology, Helmholtz-Zentrum München, German Research Center for Environmental Health, Neuherberg, 85764, Germany.
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  • Fabian J Theis, Department of Mathematics, Technische Universität München, Munich, 85748, Germany.
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  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
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  • Katri Räikkönen, Cognitive Brain Research Unit, Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland; Department of Psychology, Abo Akademi University, Turku, Finland.
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  • Elisabeth B Binder, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, 30329, USA. binder@psych.mpg.de.

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Original languageEnglish
Article number2548
JournalNature Communications
Volume10
Number of pages18
ISSN2041-1723
DOIs
Publication statusPublished - Jun 2019

    Research areas

  • BIRTH, CHILDHOOD MALTREATMENT, GENOME-WIDE, GENOTYPE, IN-UTERO, MATERNAL SMOKING, NORWEGIAN MOTHER, PREGNANCY, PRENATAL STRESS, RISK

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