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 AF. 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; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi: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

Wouter J. Peyrot, Sandra Van der Auwera, Yuri Milaneschi, Conor V. Dolan, Pamela AF. 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, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

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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 language	English
Journal	Biological psychiatry
Early online date	21 Sept 2017
DOIs	https://doi.org/10.1016/j.biopsych.2017.09.009
Publication status	E-pub ahead of print - 21 Sept 2017

Keywords

Depression
polygenic risk
childhood trauma
interaction
meta-analysis
genetics

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Does childhood trauma moderate_PEYROT_Publishedonline21September2017_GREEN AAMAccepted author manuscript, 2.03 MBLicence: CC BY-NC-ND
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Peyrot, W. J., Van der Auwera, S., Milaneschi, Y., Dolan, C. V., Madden, P. AF., Sullivan, P. F., Strohmaier, J., Ripke, S., Rietschel, M., Nivard, M. G., Mullins, N., Montgomery, G. W., Henders, A. K., Heat, A. C., Fisher, H. L., Dunn, E. C., Byrne, E. M., Air, T. A., & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2017). Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium. Biological psychiatry. Advance online publication. https://doi.org/10.1016/j.biopsych.2017.09.009

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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 = "Depression, polygenic risk, childhood trauma, interaction, meta-analysis, genetics",

author = "Peyrot, {Wouter J.} and {Van der Auwera}, Sandra and Yuri Milaneschi and Dolan, {Conor V.} and Madden, {Pamela AF.} 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 WJH.} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",

year = "2017",

month = sep,

day = "21",

doi = "10.1016/j.biopsych.2017.09.009",

language = "English",

journal = "Biological psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

}

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 & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2017, 'Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium', Biological psychiatry. https://doi.org/10.1016/j.biopsych.2017.09.009

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 AF.

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 WJH.

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

PY - 2017/9/21

Y1 - 2017/9/21

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 - Depression

KW - polygenic risk

KW - childhood trauma

KW - interaction

KW - meta-analysis

KW - genetics

U2 - 10.1016/j.biopsych.2017.09.009

DO - 10.1016/j.biopsych.2017.09.009

M3 - Article

C2 - 29129318

SN - 0006-3223

JO - Biological psychiatry

JF - Biological psychiatry

ER -

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

Abstract

Keywords

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