Genome-wide gene-environment interaction in depression: A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD

Sandra Van der Auwera, Wouter J. Peyrot, Yuri Milaneschi, Johannes Hertel, Bernhard Baune, Gerome Breen, Enda Byrne, Erin C. Dunn, Helen Fisher, Georg Homuth, Douglas Levinson, Cathryn Lewis, Natalie Mills, Niamh Mullins, Matthias Nauck, Giorgio Pistis, Martin Preisig, Marcella Rietschel, Stephan Ripke, Patrick Sullivan & 7 others Alexander Teumer, Henry Völzke, Dorret I. Boomsma, Naomi R. Wray, Brenda Penninx, Hans Grabe, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Gene by environment (GxE) interaction studies have investigated the influence of a number of candidate genes and variants for major depressive disorder (MDD) on the association between childhood trauma and MDD. Most of these studies are hypothesis driven and investigate only a limited number of SNPs in relevant pathways using differing methodological approaches. Here (1) we identified 27 genes and 268 SNPs previously associated with MDD or with GxE interaction in MDD and (2) analyzed their impact on GxE in MDD using a common approach in 3944 subjects of European ancestry from the Psychiatric Genomics Consortium who had completed the Childhood Trauma Questionnaire. (3) We subsequently used the genome-wide SNP data for a genome-wide case-control GxE model and GxE case-only analyses testing for an enrichment of associated SNPs. No genome-wide significant hits and no consistency among the signals of the different analytic approaches could be observed. This is the largest study for systematic GxE interaction analysis in MDD in subjects of European ancestry to date. Most of the known candidate genes/variants could not be supported. Thus, their impact on GxE interaction in MDD may be questionable. Our results underscore the need for larger samples, more extensive assessment of environmental exposures, and greater efforts to investigate new methodological approaches in GxE models for MDD.

Original languageEnglish
Pages (from-to)40-49
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume177
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Cite this

Van der Auwera, Sandra ; Peyrot, Wouter J. ; Milaneschi, Yuri ; Hertel, Johannes ; Baune, Bernhard ; Breen, Gerome ; Byrne, Enda ; Dunn, Erin C. ; Fisher, Helen ; Homuth, Georg ; Levinson, Douglas ; Lewis, Cathryn ; Mills, Natalie ; Mullins, Niamh ; Nauck, Matthias ; Pistis, Giorgio ; Preisig, Martin ; Rietschel, Marcella ; Ripke, Stephan ; Sullivan, Patrick ; Teumer, Alexander ; Völzke, Henry ; Boomsma, Dorret I. ; Wray, Naomi R. ; Penninx, Brenda ; Grabe, Hans ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Genome-wide gene-environment interaction in depression : A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2018 ; Vol. 177, No. 1. pp. 40-49.
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title = "Genome-wide gene-environment interaction in depression: A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD",
abstract = "Gene by environment (GxE) interaction studies have investigated the influence of a number of candidate genes and variants for major depressive disorder (MDD) on the association between childhood trauma and MDD. Most of these studies are hypothesis driven and investigate only a limited number of SNPs in relevant pathways using differing methodological approaches. Here (1) we identified 27 genes and 268 SNPs previously associated with MDD or with GxE interaction in MDD and (2) analyzed their impact on GxE in MDD using a common approach in 3944 subjects of European ancestry from the Psychiatric Genomics Consortium who had completed the Childhood Trauma Questionnaire. (3) We subsequently used the genome-wide SNP data for a genome-wide case-control GxE model and GxE case-only analyses testing for an enrichment of associated SNPs. No genome-wide significant hits and no consistency among the signals of the different analytic approaches could be observed. This is the largest study for systematic GxE interaction analysis in MDD in subjects of European ancestry to date. Most of the known candidate genes/variants could not be supported. Thus, their impact on GxE interaction in MDD may be questionable. Our results underscore the need for larger samples, more extensive assessment of environmental exposures, and greater efforts to investigate new methodological approaches in GxE models for MDD.",
keywords = "candidate genes, depression, GWAS, Psychiatric Genomics Consortium",
author = "{Van der Auwera}, Sandra and Peyrot, {Wouter J.} and Yuri Milaneschi and Johannes Hertel and Bernhard Baune and Gerome Breen and Enda Byrne and Dunn, {Erin C.} and Helen Fisher and Georg Homuth and Douglas Levinson and Cathryn Lewis and Natalie Mills and Niamh Mullins and Matthias Nauck and Giorgio Pistis and Martin Preisig and Marcella Rietschel and Stephan Ripke and Patrick Sullivan and Alexander Teumer and Henry V{\"o}lzke and Boomsma, {Dorret I.} and Wray, {Naomi R.} and Brenda Penninx and Hans Grabe and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",
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Van der Auwera, S, Peyrot, WJ, Milaneschi, Y, Hertel, J, Baune, B, Breen, G, Byrne, E, Dunn, EC, Fisher, H, Homuth, G, Levinson, D, Lewis, C, Mills, N, Mullins, N, Nauck, M, Pistis, G, Preisig, M, Rietschel, M, Ripke, S, Sullivan, P, Teumer, A, Völzke, H, Boomsma, DI, Wray, NR, Penninx, B, Grabe, H & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2018, 'Genome-wide gene-environment interaction in depression: A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD' American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 177, no. 1, pp. 40-49. https://doi.org/10.1002/ajmg.b.32593

Genome-wide gene-environment interaction in depression : A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD. / Van der Auwera, Sandra; Peyrot, Wouter J.; Milaneschi, Yuri; Hertel, Johannes; Baune, Bernhard; Breen, Gerome; Byrne, Enda; Dunn, Erin C.; Fisher, Helen; Homuth, Georg; Levinson, Douglas; Lewis, Cathryn; Mills, Natalie; Mullins, Niamh; Nauck, Matthias; Pistis, Giorgio; Preisig, Martin; Rietschel, Marcella; Ripke, Stephan; Sullivan, Patrick; Teumer, Alexander; Völzke, Henry; Boomsma, Dorret I.; Wray, Naomi R.; Penninx, Brenda; Grabe, Hans; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 177, No. 1, 01.01.2018, p. 40-49.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genome-wide gene-environment interaction in depression

T2 - A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD

AU - Van der Auwera, Sandra

AU - Peyrot, Wouter J.

AU - Milaneschi, Yuri

AU - Hertel, Johannes

AU - Baune, Bernhard

AU - Breen, Gerome

AU - Byrne, Enda

AU - Dunn, Erin C.

AU - Fisher, Helen

AU - Homuth, Georg

AU - Levinson, Douglas

AU - Lewis, Cathryn

AU - Mills, Natalie

AU - Mullins, Niamh

AU - Nauck, Matthias

AU - Pistis, Giorgio

AU - Preisig, Martin

AU - Rietschel, Marcella

AU - Ripke, Stephan

AU - Sullivan, Patrick

AU - Teumer, Alexander

AU - Völzke, Henry

AU - Boomsma, Dorret I.

AU - Wray, Naomi R.

AU - Penninx, Brenda

AU - Grabe, Hans

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

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Gene by environment (GxE) interaction studies have investigated the influence of a number of candidate genes and variants for major depressive disorder (MDD) on the association between childhood trauma and MDD. Most of these studies are hypothesis driven and investigate only a limited number of SNPs in relevant pathways using differing methodological approaches. Here (1) we identified 27 genes and 268 SNPs previously associated with MDD or with GxE interaction in MDD and (2) analyzed their impact on GxE in MDD using a common approach in 3944 subjects of European ancestry from the Psychiatric Genomics Consortium who had completed the Childhood Trauma Questionnaire. (3) We subsequently used the genome-wide SNP data for a genome-wide case-control GxE model and GxE case-only analyses testing for an enrichment of associated SNPs. No genome-wide significant hits and no consistency among the signals of the different analytic approaches could be observed. This is the largest study for systematic GxE interaction analysis in MDD in subjects of European ancestry to date. Most of the known candidate genes/variants could not be supported. Thus, their impact on GxE interaction in MDD may be questionable. Our results underscore the need for larger samples, more extensive assessment of environmental exposures, and greater efforts to investigate new methodological approaches in GxE models for MDD.

AB - Gene by environment (GxE) interaction studies have investigated the influence of a number of candidate genes and variants for major depressive disorder (MDD) on the association between childhood trauma and MDD. Most of these studies are hypothesis driven and investigate only a limited number of SNPs in relevant pathways using differing methodological approaches. Here (1) we identified 27 genes and 268 SNPs previously associated with MDD or with GxE interaction in MDD and (2) analyzed their impact on GxE in MDD using a common approach in 3944 subjects of European ancestry from the Psychiatric Genomics Consortium who had completed the Childhood Trauma Questionnaire. (3) We subsequently used the genome-wide SNP data for a genome-wide case-control GxE model and GxE case-only analyses testing for an enrichment of associated SNPs. No genome-wide significant hits and no consistency among the signals of the different analytic approaches could be observed. This is the largest study for systematic GxE interaction analysis in MDD in subjects of European ancestry to date. Most of the known candidate genes/variants could not be supported. Thus, their impact on GxE interaction in MDD may be questionable. Our results underscore the need for larger samples, more extensive assessment of environmental exposures, and greater efforts to investigate new methodological approaches in GxE models for MDD.

KW - candidate genes

KW - depression

KW - GWAS

KW - Psychiatric Genomics Consortium

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U2 - 10.1002/ajmg.b.32593

DO - 10.1002/ajmg.b.32593

M3 - Article

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SP - 40

EP - 49

JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

SN - 1552-4841

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ER -