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, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Boomsma, Dorret I., Wray, Naomi R., Penninx, Brenda and Grabe, Hans (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, 177 1: 40-49. doi:10.1002/ajmg.b.32593


Author 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
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Boomsma, Dorret I.
Wray, Naomi R.
Penninx, Brenda
Grabe, Hans
Title Genome-wide gene-environment interaction in depression: a systematic evaluation of candidate genes: the childhood trauma working-group of PGC-MDD
Journal name American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics   Check publisher's open access policy
ISSN 1552-485X
1552-4841
Publication date 2018-01-01
Year available 2017
Sub-type Article (original research)
DOI 10.1002/ajmg.b.32593
Open Access Status Not yet assessed
Volume 177
Issue 1
Start page 40
End page 49
Total pages 10
Place of publication Hoboken, NJ United States
Publisher John Wiley & Sons
Language eng
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.
Formatted 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.
Keyword GWAS
Psychiatric Genomics Consortium
Candidate genes
Depression
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01 MH081802
R01 HD042157
U01 MH109514
U24 MH068457
U01 MH109528
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 29 Nov 2017, 12:02:19 EST