Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene-environment correlation

Background Whilst genetic and environmental risk factors for schizophrenia (SCZ) and major depressive disorder (MDD) have been established, it is unclear whether exposure to environmental risk factors is genetically confounded by passive, evocative or active gene-environment correlation (rGE). Study Objective This study aims to investigate: (a) whether the genetic risk for SCZ/MDD in children is correlated with established environmental and psychosocial risk factors in two British community samples, the 1958 National Child Development Study (NCDS) and the Millennium Cohort Study (MCS), (b) whether these associations vary between both psychopathologies, and (c) whether findings differ across the two cohorts which were born 42 years apart. Methods Polygenic risk scores (PRS) from existing large genome-wide associations studies (GWAS) were applied to test the correlation between the child genetic risk for SCZ/MDD and known environmental risk factors. In addition, parental and child genetic data from MCS were used to distinguish between passive and evocative rGE. Results The child polygenic risk for SCZ and MDD was correlated with single parenthood in MCS. Moreover, the lack of father's involvement in child care was associated with the genetic risk for SCZ in NCDS. However, we also found associations between several indicators of low socioeconomic status and heightened genetic risk for MDD in children in both cohorts. Further, the genetic risk for MDD was associated with parental lack of interest in the child's education in NCDS as well as more maternal smoking and less maternal alcohol consumption during childhood in MCS. According to sensitivity analyses in MCS (controlling for parental genotype), more than half of our significant correlations reflected passive rGE. Conclusions Findings suggest that several established environmental and psychosocial risk factors for SCZ and MDD are at least partially associated with children's genetic risk for these psychiatric disorders.

Automated summary

The study found that environmental and psychosocial risk factors for schizophrenia and major depressive disorder are partially associated with children's genetic risk for these psychiatric disorders. Single-parent families and lack of father's involvement in child care are correlated with genetic risk for schizophrenia. Moreover, indicators of low socioeconomic status are associated with heightened genetic risk for major depressive disorder in children. Sensitivity analyses showed that more than half of the significant correlations reflected passive gene-environment correlation.