Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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29129318
TITLE
Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
Copyright (c) 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2017 Sep 21
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/05/21
revised 2017/09/01
accepted 2017/09/01
entrez 2017/11/14 06:00
pubmed 2017/11/14 06:00
medline 2017/11/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
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
Baune BT
Breen G
Levinson DF
Lewis CM
Martin NG
Nelson EN
Boomsma DI
Grabe HJ
Wray NR
Penninx BWJH
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Wray Naomi R NR
Ripke Stephan S
Mattheisen Manuel M
Trzaskowski Maciej M
Byrne Enda M EM
Abdellaoui Abdel A
Adams Mark J MJ
Agerbo Esben E
Air Tracy M TM
Andlauer Till F M TFM
Bacanu Silviu-Alin SA
Bækvad-Hansen Marie M
Beekman Aartjan T F ATF
Bigdeli Tim B TB
Binder Elisabeth B EB
Blackwood Douglas H R DHR
Bryois Julien J
Buttenschøn Henriette N HN
Bybjerg-Grauholm Jonas J
Cai Na N
Castelao Enrique E
Christensen Jane Hvarregaard JH
Clarke Toni-Kim TK
Coleman Jonathan R I JRI
Colodro-Conde Lucía L
Couvy-Duchesne Baptiste B
Craddock Nick N
Crawford Gregory E GE
Davies Gail G
Deary Ian J IJ
Degenhardt Franziska F
Derks Eske M EM
Direk Nese N
Dolan Conor V CV
Dunn Erin C EC
Eley Thalia C TC
Escott-Price Valentina V
Farnush
Kiadeh Farhadi Hassan FH
Finucane Hilary K HK
Forstner Andreas J AJ
Frank Josef J
Gaspar Héléna A HA
Gill Michael M
Goes Fernando S FS
Gordon Scott D SD
Grove Jakob J
Hall Lynsey S LS
Hansen Christine Søholm CS
Hansen Thomas F TF
Herms Stefan S
Hicki Ian B IB
Hoffmann Per P
Homuth Georg G
Horn Carsten C
Hottenga Jouke-Jan JJ
Hougaard David M DM
Ising Marcus M
Jansen Rick R
Jorgenson Eric E
Knowles James A JA
Kohane Isaac S IS
Kraft Julia J
Kretzschmar Warren W WW
Krogh Jesper J
Kutalik Zoltán Z
Li Yihan Y
Lind Penelope A PA
MacIntyre Donald J DJ
MacKinnon Dean F DF
Maier Robert M RM
Maier Wolfgang W
Marchini Jonathan J
Mbarek Hamdi H
McGrath Patrick P
McGuffin Peter P
Medland Sarah E SE
Mehta Divya D
Middeldorp Christel M CM
Mihailov Evelin E
Milaneschi Yuri Y
Milani Lili L
Mondimore Francis M FM
Montgomery Grant W GW
Mostafavi Sara S
Mullins Niamh N
Nauck Matthias M
Ng Bernard B
Nivard Michel G MG
Nyholt Dale R DR
O'Reilly Paul F PF
Oskarsson Hogni H
Owen Michael J MJ
Painter Jodie N JN
Pedersen Carsten Bøcker CB
Pedersen Marianne Giørtz MG
Peterson Roseann E RE
Pettersson Erik E
Peyrot Wouter J WJ
Pistis Giorgio G
Posthuma Danielle D
Quiroz Jorge A JA
Qvist Per P
Rice John P JP
Riley Brien P BP
Rivera Margarita M
Mirza Saira Saeed SS
Schoevers Robert R
Schulte Eva C EC
Shen Ling L
Shi Jianxin J
Shyn Stanley I SI
Sigurdsson Engilbert E
Sinnamon Grant C B GCB
Smit Johannes H JH
Smith Daniel J DJ
Stefansson Hreinn H
Steinberg Stacy S
Streit Fabian F
Strohmaier Jana J
Tansey Katherine E KE
Teismann Henning H
Teumer Alexander A
Thompson Wesley W
Thomson Pippa A PA
Thorgeirsson Thorgeir E TE
Traylor Matthew M
Treutlein Jens J
Trubetskoy Vassily V
Uitterlinden André G AG
Umbricht Daniel D
Van der Auwera Sandra S
van Hemert Albert M AM
Viktorin Alexander A
Visscher Peter M PM
Wang Yunpeng Y
Webb Bradley T BT
Weinsheimer Shantel Marie SM
Wellmann Jürgen J
Willemsen Gonneke G
Witt Stephanie H SH
Wu Yang Y
Xi Hualin S HS
Yang Jian J
Zhang Futao F
Arolt Volker V
Baune Bernhard T BT
Berger Klaus K
Boomsma Dorret I DI
Cichon Sven S
Dannlowski Udo U
de Geus E J C EJC
DePaulo J Raymond JR
Domenici Enrico E
Domschke Katharina K
Esko Tõnu T
Grabe Hans J HJ
Hamilton Steven P SP
Hayward Caroline C
Heath Andrew C AC
Kendler Kenneth S KS
Kloiber Stefan S
Lewis Glyn G
Li Qingqin S QS
Lucae Susanne S
Madden Pamela A F PAF
Magnusson Patrik K PK
Martin Nicholas G NG
McIntosh Andrew M AM
Metspalu Andres A
Mors Ole O
Mortensen Preben Bo PB
Müller-Myhsok Bertram B
Nordentoft Merete M
Nöthen Markus M MM
O'Donovan Michael C MC
Paciga Sara A SA
Pedersen Nancy L NL
Penninx Brenda W J H BWJH
Perlis Roy H RH
Porteous David J DJ
Potash James B JB
Preisig Martin M
Rietschel Marcella M
Schaefer Catherine C
Schulze Thomas G TG
Smoller Jordan W JW
Stefansson Kari K
Tiemeier Henning H
Uher Rudolf R
Völzke Henry H
Weissman Myrna M MM
Werge Thomas T
Lewis Cathryn M CM
Levinson Douglas F DF
Breen Gerome G
Børglum Anders D AD
Sullivan Patrick F PF
JOURNAL
VOLUME:
ISSUE:
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2017
MONTH: Sep
DAY: 21
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1873-2402
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Biol Psychiatry
COUNTRY: United States
ISSNLINKING: 0006-3223
NLMUNIQUEID: 0213264
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Childhood trauma
Depression
Genetics
Interaction
Meta-analysis
Polygenic risk
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's