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, Bernhard T Baune, Gerome Breen & 10 others Douglas F Levinson, Cathryn M Lewis, Nick G Martin, Elliot N Nelson, Dorret I Boomsma, Hans J Grabe, Naomi R Wray, Brenda W J H Penninx, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, J.J. Hottenga

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), 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
Pages (from-to)138-147
JournalBiological Psychiatry
Volume84
Issue number2
DOIs
Publication statusPublished - 1 Jul 2018

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

Keywords

  • Journal Article

Cite this

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 ; Baune, Bernhard T ; Breen, Gerome ; Levinson, Douglas F ; Lewis, Cathryn M ; Martin, Nick G ; Nelson, Elliot N ; Boomsma, Dorret I ; Grabe, Hans J ; Wray, Naomi R ; Penninx, Brenda W J H ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Hottenga, J.J. / 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{d4187cbdd6984114a7101a128672b906,
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), 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.",
keywords = "Journal Article",
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 Baune, {Bernhard T} and Gerome Breen and Levinson, {Douglas F} and Lewis, {Cathryn M} and Martin, {Nick G} and Nelson, {Elliot N} and Boomsma, {Dorret I} and Grabe, {Hans J} and Wray, {Naomi R} and Penninx, {Brenda W J H} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and J.J. Hottenga",
note = "Copyright {\circledC} 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "7",
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doi = "10.1016/j.biopsych.2017.09.009",
language = "English",
volume = "84",
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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, Baune, BT, Breen, G, Levinson, DF, Lewis, CM, Martin, NG, Nelson, EN, Boomsma, DI, Grabe, HJ, Wray, NR, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium & Hottenga, JJ 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; Baune, Bernhard T; Breen, Gerome; Levinson, Douglas F; Lewis, Cathryn M; Martin, Nick G; Nelson, Elliot N; Boomsma, Dorret I; Grabe, Hans J; Wray, Naomi R; Penninx, Brenda W J H; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Hottenga, J.J.

In: Biological Psychiatry, Vol. 84, No. 2, 01.07.2018, p. 138-147.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Does Childhood Trauma Moderate Polygenic Risk for Depression?

T2 - 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 - Baune, Bernhard T

AU - Breen, Gerome

AU - Levinson, Douglas F

AU - Lewis, Cathryn M

AU - Martin, Nick G

AU - Nelson, Elliot N

AU - Boomsma, Dorret I

AU - Grabe, Hans J

AU - Wray, Naomi R

AU - Penninx, Brenda W J H

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

AU - Hottenga, J.J.

N1 - Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2018/7/1

Y1 - 2018/7/1

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), 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.

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), 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.

KW - Journal Article

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 -