Depression is not due to interaction of genetics and childhood trauma -- study of 5,765 subjects from the Psychiatric Genomics Consortium

Does childhood trauma moderate polygenic risk for depression? A meta-analysis of 5,765 subjects from the Psychiatric Genomics Consortium. Wouter J. Peyrot, et al. Biological Psychiatry, https://doi.org/10.1016/j.biopsych.2017.09.009

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 (PRS) and CT, albeit in opposing directions. This study aims to meta-analyze MDD-PRSxCT interaction results across these two and other cohorts, while applying more accurate PRS based on a larger discovery sample.

Methods and Materials: Data were combined from 3,024 MDD cases and 2,741 controls from nine cohorts contributing to the MDD Working Group of the Psychiatric Genomics Consortium. MDD-PRS were based on a discovery sample of approximately 110,000 independent individuals. CT was assessed as exposure to sexual or physical abuse during childhood. In a subset of 1957 cases and 2002 controls, a more detailed 5-domain measure additionally included emotional abuse, physical neglect and emotional neglect.

Results: MDD was associated with the MDD-PRS (OR=1.24, p=3.6e-5, R2=1.18%) and with CT (OR=2.63, p=3.5e-18 and OR=2.62, p=1.4e-5 for the 2- and 5-domain measures respectively). No interaction was found between MDD-PRS and the 2-domain and 5-domain CT measure (OR=1.00, p=0.89 and OR=1.05, p=0.66).

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.