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

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticle

Abstract

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, R2 = 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 (US)
Pages (from-to)138-147
Number of pages10
JournalBiological Psychiatry
Volume84
Issue number2
DOIs
StatePublished - Jul 15 2018

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Major Depressive Disorder
Genomics
Psychiatry
Meta-Analysis
Depression
Wounds and Injuries
Odds Ratio
Genetic Heterogeneity
Sex Offenses
Genome

Keywords

  • Childhood trauma
  • Depression
  • Genetics
  • Interaction
  • Meta-analysis
  • Polygenic risk

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. / Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Biological Psychiatry, Vol. 84, No. 2, 15.07.2018, p. 138-147.

Research output: Contribution to journalArticle

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. In: Biological Psychiatry. 2018 ; Vol. 84, No. 2. pp. 138-147.
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title = "Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium",
abstract = "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, R2 = 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.",
keywords = "Childhood trauma, Depression, Genetics, Interaction, Meta-analysis, Polygenic risk",
author = "{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Peyrot, {Wouter J.} and {Van der Auwera}, Sandra and Yuri Milaneschi and Dolan, {Conor V.} and Madden, {Pamela A.F.} and Sullivan, {Patrick F.} and Jana Strohmaier and Stephan Ripke and Marcella Rietschel and Nivard, {Michel G.} and Niamh Mullins and Montgomery, {Grant W.} and Henders, {Anjali K.} and Heat, {Andrew C.} and Fisher, {Helen L.} and Dunn, {Erin C.} and Byrne, {Enda M.} and Air, {Tracy A.} and Wray, {Naomi R.} and Manuel Mattheisen and Maciej Trzaskowski and Abdel Abdellaoui and Adams, {Mark J.} and Esben Agerbo and Air, {Tracy M.} and Andlauer, {Till F.M.} and Bacanu, {Silviu Alin} and Marie B{\ae}kvad-Hansen and Beekman, {Aartjan T.F.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Blackwood, {Douglas H.R.} and Julien Bryois and Buttensch{\o}n, {Henriette N.} and Jonas Bybjerg-Grauholm and Na Cai and Enrique Castelao and Christensen, {Jane Hvarregaard} and Clarke, {Toni Kim} and Coleman, {Jonathan R.I.} and Luc{\'i}a Colodro-Conde and Baptiste Couvy-Duchesne and Nick Craddock and Crawford, {Gregory E.} and Gail Davies and Goes, {Fernando S} and Mackinnon, {Dean F} and Mondimore, {Francis M} and Depaulo, {J Raymond} and Potash, {James Bennett}",
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TY - JOUR

T1 - Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Peyrot, Wouter J.

AU - Van der Auwera, Sandra

AU - Milaneschi, Yuri

AU - Dolan, Conor V.

AU - Madden, Pamela A.F.

AU - Sullivan, Patrick F.

AU - Strohmaier, Jana

AU - Ripke, Stephan

AU - Rietschel, Marcella

AU - Nivard, Michel G.

AU - Mullins, Niamh

AU - Montgomery, Grant W.

AU - Henders, Anjali K.

AU - Heat, Andrew C.

AU - Fisher, Helen L.

AU - Dunn, Erin C.

AU - Byrne, Enda M.

AU - Air, Tracy A.

AU - Wray, Naomi R.

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Blackwood, Douglas H.R.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Coleman, Jonathan R.I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Goes, Fernando S

AU - Mackinnon, Dean F

AU - Mondimore, Francis M

AU - Depaulo, J Raymond

AU - Potash, James Bennett

PY - 2018/7/15

Y1 - 2018/7/15

N2 - 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, R2 = 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.

AB - 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, R2 = 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.

KW - Childhood trauma

KW - Depression

KW - Genetics

KW - Interaction

KW - Meta-analysis

KW - Polygenic risk

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