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Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium

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  • Wouter J Peyrot, VU University, Amsterdam , Netherlands
  • Sandra Van der Auwera, Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
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  • Yuri Milaneschi, Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
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  • Conor V Dolan, Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands.
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  • Pamela A F Madden, Department of Psychiatry, Washington University Medical School, St. Louis, Missouri.
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  • Patrick F Sullivan, Department of Psychiatry,University of North Carolina at Chapel Hill,Chapel Hill,NC,USA.
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  • Jana Strohmaier, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
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  • Stephan Ripke, Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Marcella Rietschel, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
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  • Michel G Nivard, Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands.
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  • Niamh Mullins, MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Grant W Montgomery, Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
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  • Anjali K Henders, Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
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  • Andrew C Heat, Department of Psychiatry, Washington University Medical School, St. Louis, Missouri.
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  • Helen L Fisher, MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Erin C Dunn, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
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  • Enda M Byrne, University of Queensland, Australia
  • Tracy A Air, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
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  • Bernhard T Baune, Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
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  • Gerome Breen, MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Douglas F Levinson, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
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  • Cathryn M Lewis, MRC-SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
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  • Nick G Martin, Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
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  • Elliot N Nelson, Department of Psychiatry, Washington University Medical School, St. Louis, Missouri.
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  • Dorret I Boomsma, Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands.
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  • Hans J Grabe, Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
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  • Naomi R Wray, Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
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  • Brenda W J H Penninx, Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
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  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

BACKGROUND: The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts showed evidence for interaction between polygenic risk scores (PRSs) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRS × CT interaction results across these two and other cohorts, while applying more accurate PRSs based on a larger discovery sample.

METHODS: Data were combined from 3024 MDD cases and 2741 control subjects from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of ∼110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 control subjects, a more detailed five-domain measure additionally included emotional abuse, physical neglect, and emotional neglect.

RESULTS: MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10(-5), R(2) = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10(-18) and OR = 2.62, p = 1.4 ×10(-5) for the two- and five-domain measures, respectively). No interaction was found between MDD-PRS and the two-domain and five-domain CT measure (OR = 1.00, p = .89 and OR = 1.05, p = .66).

CONCLUSIONS: No meta-analytic evidence for interaction between MDD-PRS and CT was found. This suggests that the previously reported interaction effects, although both statistically significant, can best be interpreted as chance findings. Further research is required, but this study suggests that the genetic heterogeneity of MDD is not attributable to genome-wide moderation of genetic effects by CT.

Original languageEnglish
JournalBiological Psychiatry
Volume84
Issue2
Pages (from-to)138-147
ISSN0006-3223
DOIs
Publication statusPublished - 2018

    Research areas

  • Journal Article

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