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

Wouter J. Peyrot, Sandra Van der Auwera, Yuri Milaneschi, Conor V. Dolan, Pamela A.F. Madden, Patrick F. Sullivan, Jana Strohmaier, Stephan Ripke, Marcella Rietschel, Michel G. Nivard, Niamh Mullins, Grant W. Montgomery, Anjali K. Henders, Andrew C. Heat, Helen L. Fisher, Erin C. Dunn, Enda M. Byrne, Tracy A. Air, Naomi R. Wray, Stephan Ripke & 28 others Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy M. Air, Brenda W.J.H. Penninx, Silviu Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Elisabeth B. Binder, Douglas H.R. Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Rick Jansen, Christel M. Middeldorp, Yuri Milaneschi, Danielle Posthuma, Robert Schoevers, Johannes H. Smit, E. J.C. de Geus, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticleAcademicpeer-review

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
Pages (from-to)138-147
Number of pages10
JournalBiological Psychiatry
Volume84
Issue number2
DOIs
Publication statusPublished - 15 Jul 2018

Cite this

Peyrot, W. J., Van der Auwera, S., Milaneschi, Y., Dolan, C. V., Madden, P. A. F., Sullivan, P. F., ... Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2018). Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. Biological Psychiatry, 84(2), 138-147. https://doi.org/10.1016/j.biopsych.2017.09.009
Peyrot, Wouter J. ; Van der Auwera, Sandra ; Milaneschi, Yuri ; Dolan, Conor V. ; Madden, Pamela A.F. ; Sullivan, Patrick F. ; Strohmaier, Jana ; Ripke, Stephan ; Rietschel, Marcella ; Nivard, Michel G. ; Mullins, Niamh ; Montgomery, Grant W. ; Henders, Anjali K. ; Heat, Andrew C. ; Fisher, Helen L. ; Dunn, Erin C. ; Byrne, Enda M. ; Air, Tracy A. ; Wray, Naomi R. ; Ripke, Stephan ; Mattheisen, Manuel ; Trzaskowski, Maciej ; Byrne, Enda M. ; Abdellaoui, Abdel ; Adams, Mark J. ; Agerbo, Esben ; Air, Tracy M. ; Penninx, Brenda W.J.H. ; Bacanu, Silviu Alin ; Bækvad-Hansen, Marie ; Beekman, Aartjan T.F. ; Bigdeli, Tim B. ; Binder, Elisabeth B. ; Blackwood, Douglas H.R. ; Bryois, Julien ; Buttenschøn, Henriette N. ; Bybjerg-Grauholm, Jonas ; Cai, Na ; Castelao, Enrique ; Christensen, Jane Hvarregaard ; Jansen, Rick ; Middeldorp, Christel M. ; Milaneschi, Yuri ; Posthuma, Danielle ; Schoevers, Robert ; Smit, Johannes H. ; de Geus, E. J.C. ; 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.
@article{6583ab564a0c4102a36e364420f38350,
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 = "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 Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, {Enda M.} and Abdel Abdellaoui and Adams, {Mark J.} and Esben Agerbo and Air, {Tracy M.} and Penninx, {Brenda W.J.H.} 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 Rick Jansen and Middeldorp, {Christel M.} and Yuri Milaneschi and Danielle Posthuma and Robert Schoevers and Smit, {Johannes H.} and {de Geus}, {E. J.C.} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",
year = "2018",
month = "7",
day = "15",
doi = "10.1016/j.biopsych.2017.09.009",
language = "English",
volume = "84",
pages = "138--147",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "2",

}

Peyrot, WJ, Van der Auwera, S, Milaneschi, Y, Dolan, CV, Madden, PAF, Sullivan, PF, Strohmaier, J, Ripke, S, Rietschel, M, Nivard, MG, Mullins, N, Montgomery, GW, Henders, AK, Heat, AC, Fisher, HL, Dunn, EC, Byrne, EM, Air, TA, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Penninx, BWJH, Bacanu, SA, Bækvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Binder, EB, Blackwood, DHR, Bryois, J, Buttenschøn, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Jansen, R, Middeldorp, CM, Milaneschi, Y, Posthuma, D, Schoevers, R, Smit, JH, de Geus, EJC & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2018, 'Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium' Biological Psychiatry, vol. 84, no. 2, pp. 138-147. https://doi.org/10.1016/j.biopsych.2017.09.009

Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. / Peyrot, Wouter J.; Van der Auwera, Sandra; Milaneschi, Yuri; Dolan, Conor V.; Madden, Pamela A.F.; Sullivan, Patrick F.; Strohmaier, Jana; Ripke, Stephan; Rietschel, Marcella; Nivard, Michel G.; Mullins, Niamh; Montgomery, Grant W.; Henders, Anjali K.; Heat, Andrew C.; Fisher, Helen L.; Dunn, Erin C.; Byrne, Enda M.; Air, Tracy A.; Wray, Naomi R.; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M.; Abdellaoui, Abdel; Adams, Mark J.; Agerbo, Esben; Air, Tracy M.; Penninx, Brenda W.J.H.; Bacanu, Silviu Alin; Bækvad-Hansen, Marie; Beekman, Aartjan T.F.; Bigdeli, Tim B.; Binder, Elisabeth B.; Blackwood, Douglas H.R.; Bryois, Julien; Buttenschøn, Henriette N.; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Jansen, Rick; Middeldorp, Christel M.; Milaneschi, Yuri; Posthuma, Danielle; Schoevers, Robert; Smit, Johannes H.; de Geus, E. J.C.; 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 journalArticleAcademicpeer-review

TY - JOUR

T1 - Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From 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 - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Penninx, Brenda W.J.H.

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 - Jansen, Rick

AU - Middeldorp, Christel M.

AU - Milaneschi, Yuri

AU - Posthuma, Danielle

AU - Schoevers, Robert

AU - Smit, Johannes H.

AU - de Geus, E. J.C.

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

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

UR - http://www.scopus.com/inward/record.url?scp=85033387316&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2017.09.009

DO - 10.1016/j.biopsych.2017.09.009

M3 - Article

VL - 84

SP - 138

EP - 147

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 2

ER -