title: Effect of polygenic risk scores on depression in childhood trauma.
abstract: BACKGROUND
  Research on gene × environment interaction in major depressive disorder (MDD) has thus far primarily focused on candidate genes, although genetic effects are known to be polygenic.
  
  
  OBJECTIVE
  To test whether the effect of polygenic risk scores on MDD is moderated by childhood trauma.
  
  
  METHODS
  The study sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340 screened controls from The Netherlands. Chronic or remitted episodes (severe MDD) were present in 956 participants. The occurrence of childhood trauma was assessed with the Childhood Trauma Interview and the polygenic risk scores were based on genome-wide meta-analysis results from the Psychiatric Genomics Consortium.
  
  
  RESULTS
  The polygenic risk scores and childhood trauma independently affected MDD risk, and evidence was found for interaction as departure from both multiplicativity and additivity, indicating that the effect of polygenic risk scores on depression is increased in the presence of childhood trauma. The interaction effects were similar in predicting all MDD risk and severe MDD risk, and explained a proportion of variation in MDD risk comparable to the polygenic risk scores themselves.
  
  
  CONCLUSIONS
  The interaction effect found between polygenic risk scores and childhood trauma implies that (1) studies on direct genetic effect on MDD gain power by focusing on individuals exposed to childhood trauma, and that (2) individuals with both high polygenic risk scores and exposure to childhood trauma are particularly at risk for developing MDD.
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: Peyrot
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Abdel
authors.initials: A
authors.lastname: Abdellaoui
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Jouke J
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Wouter J. Peyrot, MD, Yuri Milaneschi, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands; Abdel Abdellaoui, MSc, Department of Biological Psychology, VU University Amsterdam, and Neuroscience Campus Amsterdam, Amsterdam, The Netherlands; Patrick F. Sullivan, PhD, Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, North Carolina, USA; Jouke J. Hottenga, PhD, Dorret I. Boomsma, PhD, Department of Biological Psychology, VU University Amsterdam; Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands; Brenda W. J. H. Penninx, PhD, Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute for Health and Care Research, VU University Medical Center & GGZ inGeest, Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
mesh_terms: D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000706:statistics & numerical data*; D016022:Case-Control Studies; D002648:Child; D002649:Child Abuse / Q000706:statistics & numerical data*; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors