|
|
| PMID |
|
|
| 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 |
|
| 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. 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 |
|
| 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. 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. MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10 , R = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10 and OR = 2.62, p = 1.4 ×10 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 |
|
| 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. 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. MDD was associated with the MDD-PRS (odds ratio [OR] = 1.24, p = 3.6 × 10 , R = 1.18%) and with CT (OR = 2.63, p = 3.5 × 10 and OR = 2.62, p = 1.4 ×10 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). 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 © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2017/05/21 |
| revised |
2017/09/01 |
| accepted |
2017/09/01 |
| pubmed |
2017/11/14 06:00 |
| medline |
2019/10/08 06:00 |
| entrez |
2017/11/14 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Peyrot WJ |
|
Peyrot |
Wouter J |
WJ |
|
Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands. Electronic address: peyrot.w@gmail.com. |
| Van der Auwera S |
|
Van der Auwera |
Sandra |
S |
|
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
| Milaneschi Y |
|
Milaneschi |
Yuri |
Y |
|
Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands. |
| Dolan CV |
|
Dolan |
Conor V |
CV |
|
Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands. |
| Madden PAF |
|
Madden |
Pamela A F |
PAF |
|
Department of Psychiatry, Washington University Medical School, St. Louis, Missouri. |
| Sullivan PF |
|
Sullivan |
Patrick F |
PF |
|
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. |
| Strohmaier J |
|
Strohmaier |
Jana |
J |
|
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany. |
| Ripke S |
|
Ripke |
Stephan |
S |
|
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts. |
| Rietschel M |
|
Rietschel |
Marcella |
M |
|
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany. |
| Nivard MG |
|
Nivard |
Michel G |
MG |
|
Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands. |
| Mullins N |
|
Mullins |
Niamh |
N |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. |
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. |
| Henders AK |
|
Henders |
Anjali K |
AK |
|
Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. |
| Heat AC |
|
Heat |
Andrew C |
AC |
|
Department of Psychiatry, Washington University Medical School, St. Louis, Missouri. |
| Fisher HL |
|
Fisher |
Helen L |
HL |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. |
| Dunn EC |
|
Dunn |
Erin C |
EC |
|
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. |
| Byrne EM |
|
Byrne |
Enda M |
EM |
|
Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. |
| Air TA |
|
Air |
Tracy A |
TA |
|
Discipline of Psychiatry, University of Adelaide, Adelaide, Australia. |
|
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium |
|
|
|
|
|
| Baune BT |
|
Baune |
Bernhard T |
BT |
|
Discipline of Psychiatry, University of Adelaide, Adelaide, Australia. |
| Breen G |
|
Breen |
Gerome |
G |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. |
| Levinson DF |
|
Levinson |
Douglas F |
DF |
|
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. |
| Lewis CM |
|
Lewis |
Cathryn M |
CM |
|
Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK. |
| Martin NG |
|
Martin |
Nick G |
NG |
|
Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, Australia. |
| Nelson EN |
|
Nelson |
Elliot N |
EN |
|
Department of Psychiatry, Washington University Medical School, St. Louis, Missouri. |
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
Department of Biological Psychology, VU University Medical Center, Amsterdam, the Netherlands. |
| Grabe HJ |
|
Grabe |
Hans J |
HJ |
|
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
| Wray NR |
|
Wray |
Naomi R |
NR |
|
Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia. |
| Penninx BWJH |
|
Penninx |
Brenda W J H |
BWJH |
|
Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands. |
|
| 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: 84 |
| ISSUE: 2 |
| TITLE: Biological psychiatry |
| ISOABBREVIATION: Biol Psychiatry |
| YEAR: 2018 |
| MONTH: 07 |
| DAY: 15 |
| 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 |
| Meta-Analysis |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| ErratumIn |
Biol Psychiatry. 2018 Dec 1;84(11):857 |
30409266 |
|
| CommentIn |
Biol Psychiatry. 2018 Jul 15;84(2):82-84 |
31178063 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| U01 MH085520 |
NIMH NIH HHS |
United States |
| R01 MH081802 |
NIMH NIH HHS |
United States |
| MR/N015746/1 |
Medical Research Council |
United Kingdom |
| K01 MH102403 |
NIMH NIH HHS |
United States |
| U01 MH109514 |
NIMH NIH HHS |
United States |
| U01 MH109528 |
NIMH NIH HHS |
United States |
| S10 OD018164 |
NIH HHS |
United States |
| R01 MH113930 |
NIMH NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
| KEYWORD |
| Childhood trauma |
| Depression |
| Genetics |
| Interaction |
| Meta-analysis |
| Polygenic risk |
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Adult Survivors of Child Abuse |
psychology |
| Case-Control Studies |
psychology |
| Child |
psychology |
| Child Abuse |
psychology |
| Depressive Disorder, Major |
genetics |
| Female |
genetics |
| Gene-Environment Interaction |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Humans |
genetics |
| Logistic Models |
genetics |
| Male |
genetics |
| Multifactorial Inheritance |
genetics |
| Psychiatric Status Rating Scales |
genetics |
| Risk Assessment |
genetics |
| Risk Factors |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
|
| OTHER ID's |
|
|
|
