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

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

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Vagelos College of Physicians and Surgeons

Producción científica › revisión exhaustiva

77 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	138-147
Número de páginas	10
Publicación	Biological Psychiatry
Volumen	84
N.º	2
DOI	https://doi.org/10.1016/j.biopsych.2017.09.009
Estado	Published - jul. 15 2018

Financiación

This study was funded by the Australian National Health and Medical Research Council Grant Nos. 1078901 and 1087889 (to NRW) and Fellowship No. 1053639 (to EMB). The NESDA was funded by the Netherlands Organization for Scientific Research (MagW/ZonMW Grant Nos. 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20; Spinozapremie Grant No. 56-464-14192; Geestkracht program Grant No. 10-000-1002); the Center for Medical Systems Biology (NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure, VU Institutes for Health and Care Research and Neuroscience Campus Amsterdam, Netherlands Bioinformatics Centre/BioAssist/RK (Grant No. 2008.024); the European Science Foundation (Grant No. EU/QLRT-2001-01254); the European Community's Seventh Framework Program (Grant No. FP7/2007-2013); European Network for Genetic and Genomic Epidemiology (ENGAGE) (Grant No. HEALTH-F4-2007-201413); and the European Science Council (European Research Council Grant No. 230374). Genotyping was funded in part by the Genetic Association Information Network of the Foundation for the US National Institutes of Health, and analysis was supported by grants from Genetic Association Information Network and the National Institute of Mental Health (Grant No. MH081802). COFAMS was supported by a grant from the National Health and Medical Research Council (Grant No. APP 1060524 to BTB). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (Grant Nos. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide data analyses in SHIP have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. Genome-wide genotyping in SHIP-TREND-0 was supported by the Federal Ministry of Education and Research (Grant No. 03ZIK012). This work was also funded by the German Research Foundation (Grant No. GR 1912/5-1). In addition, this work was supported by the German Federal Ministry of Education and Research within the framework of the e:Med research and funding concept (Integrament; Grant No. 01ZX1314E). DIB received Royal Netherlands Academy of Science Professor Award PAH/6635. MR received funding from the German Federal Ministry of Education and Research within the context of the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders; Grant No. 01ZX1314G). The German Research Foundation within the context of Forschergruppe 2107 awarded Grant Nos. RI908/11-1 (to MR) and WI 3439/3-1 (to SHW). This report represents independent research partially funded by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. The RADIANT studies were funded by a joint grant from the UK Medical Research Council (Grant No. G0701420) and GlaxoSmithKline and by the National Institute for Health Research Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service Foundation Trust and Institute of Psychiatry, Psychology, and Neuroscience, King's College London. The European Community's Seventh Framework Programme under the Marie Curie Industry-Academia Partnership and Pathways awarded Grant No. 286213 (to NM and CML). The National Institute of Mental Health provided Grant No. 1K01MH102403 (to ECD). Macquarie University provided Fellows Award No. MQ14F40 (to HLF).

Financiadores	Número del financiador
Biobanking and Biomolecular Resources Research Infrastructure
European Network for Genetic and Genomic Epidemiology	HEALTH-F4-2007-201413
European Science Council
Federal State of Mecklenburg-West Pomerania	03ZIK012
Marie Curie Industry-Academia Partnership and Pathways	286213, 1K01MH102403
Ministry of Cultural Affairs
National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust
National Institute for Health Research Biomedical Research Centre for Mental Health
Netherlands Bioinformatics Centre/BioAssist/RK	2008.024
Social Ministry of the Federal State of Mecklenburg-West Pomerania
South London and Maudsley National Health Service Foundation Trust
VU Institutes for Health and Care Research and Neuroscience Campus Amsterdam
National Institutes of Health
National Institute of Mental Health	K01MH102403, MH081802
GlaxoSmithKline
King’s College London
Seventh Framework Programme	FP7/2007-2013
Medical Research Council	G0701420
King's College London
European Research Council	230374
European Science Foundation	EU/QLRT-2001-01254
National Health and Medical Research Council	1078901, 1053639, 1087889, APP 1060524
Deutsche Forschungsgemeinschaft	GR 1912/5-1
Bundesministerium für Bildung und Forschung	01ZZ0403, 01ZX1314E, WI 3439/3-1, 01ZX1314G, 01ZZ0103, 01ZZ9603, RI908/11-1
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	480-04-004, 912-100-20, 904-61-090, 400-05-717, 904-61-193, 985-10-002, 10-000-1002, 56-464-14192
Seventh Framework Programme
Centre for Medical Systems Biology

ASJC Scopus Subject Areas

Biological Psychiatry

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10.1016/j.biopsych.2017.09.009

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@article{8333ababc4cf4ad59c06b870fbe174e4,

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.",

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 Deary, {Ian J.} and Franziska Degenhardt and Derks, {Eske M.} and Nese Direk and Weissman, {Myrna M.}",

note = "Publisher Copyright: {\textcopyright} 2017 Society of Biological Psychiatry",

year = "2018",

month = jul,

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",

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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 - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Weissman, Myrna M.

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 , 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.

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

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ASJC Scopus Subject Areas

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