Journal
BIOLOGICAL PSYCHIATRY
Volume 84, Issue 2, Pages 138-147Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2017.09.009
Keywords
Childhood trauma; Depression; Genetics; Interaction; Meta-analysis; Polygenic risk
Categories
Funding
- Australian National Health and Medical Research Council [1078901, 1087889, 1053639]
- Netherlands Organization for Scientific Research (MagW/ZonMW Grant) [904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, 912-100-20]
- Spinozapremie Grant [56-464-14192]
- Geestkracht program [10-000-1002]
- Center for Medical Systems Biology (NWO Genomics)
- Biobanking and Biomolecular Resources Research Infrastructure
- VU Institutes for Health and Care Research and Neuroscience Campus Amsterdam
- Netherlands Bioinformatics Centre/BioAssist/RK [2008.024]
- European Science Foundation [EU/QLRT-2001-01254]
- European Community's Seventh Framework Program [FP7/2007-2013]
- European Network for Genetic and Genomic Epidemiology (ENGAGE) [HEALTH-F4-2007-201413]
- European Science Council (European Research Council Grant) [230374]
- Genetic Association Information Network of the Foundation
- Genetic Association Information Network
- National Institute of Mental Health [MH081802, 1K01MH102403]
- National Health and Medical Research Council [APP 1060524]
- Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]
- Ministry of Cultural Affairs
- Social Ministry of the Federal State of Mecklenburg-West Pomerania
- Siemens Healthineers, Erlangen, Germany
- Federal State of Mecklenburg-West Pomerania
- German Research Foundation [GR 1912/5-1, 2107, RI908/11-1, WI 3439/3-1]
- German Federal Ministry of Education and Research [01ZX1314E, 01ZX1314G]
- Royal Netherlands Academy of Science Professor Award [PAH/6635]
- National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust
- King's College London
- UK Medical Research Council [G0701420]
- GlaxoSmithKline
- National Institute for Health Research Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service Foundation Trust
- Institute of Psychiatry, Psychology, and Neuroscience, King's College London
- European Community's Seventh Framework Programme under the Marie Curie Industry-Academia Partnership and Pathways [286213]
- Macquarie University [MQ14F40]
- European Research Council (ERC) [230374] Funding Source: European Research Council (ERC)
- MRC [MR/N015746/1] Funding Source: UKRI
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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 3 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 w110,000 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 x 10(-5), R-2 = 1.18%) and with CT (OR = 2.63, p = 3.5 x 10(-18) and OR = 2.62, p = 1.4 x 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.
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