TY - JOUR
T1 - Does Childhood Trauma Moderate Polygenic Risk for Depression?
T2 - A Meta-analysis of 5765 Subjects From 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 - Baune, Bernhard T
AU - Breen, Gerome
AU - Levinson, Douglas F
AU - Lewis, Cathryn M
AU - Martin, Nick G
AU - Nelson, Elliot N
AU - Boomsma, Dorret I
AU - Grabe, Hans J
AU - Wray, Naomi R
AU - Penninx, Brenda W J H
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Buttenschøn, Henriette Nørmølle
AU - Mortensen, Preben Bo
AU - Grove, Jakob
AU - Børglum, Anders
AU - Qvist, Per
AU - Christensen, Jane Hvarregaard
N1 - Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PY - 2018
Y1 - 2018
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.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85033387316&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2017.09.009
DO - 10.1016/j.biopsych.2017.09.009
M3 - Journal article
C2 - 29129318
SN - 0006-3223
VL - 84
SP - 138
EP - 147
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 2
ER -