Polygenic risk associations with developmental and mental health outcomes in childhood and adolescence: A systematic review

BACKGROUND: Neurodevelopmental and mental health disorders in childhood constitute an emerging global concern, with adverse sequelae which span children’s physical, psychological and social well-being. The aetiology of these disorders is likely complex, multifactorial and polygenic. Polygenic risk scores (PRS), an estimate of an individual’s genetic liability toward a disorder, have been increasingly used in psychiatric research to explore genetic associations with disorders of interest. However, limited work delineates polygenic associations with development and mental health in childhood populations. We aimed to systematically review existing literature on associations between genetic risk (as measured by PRS) and neurodevelopmental and mental health outcomes in childhood and adolescence. METHODS: Following the recommended Preferred Reporting Items for Meta-Analyses (PRISMA) guidelines, databases were searched using key search terms. The search commenced in March 2021 and concluded in June 2021. The studies eligible for inclusion were full-text articles investigating polygenic risk associations with neurodevelopmental and/or mental health outcomes in childhood or adolescence. RESULTS: Fourteen studies were eligible for inclusion in this systematic review. The association between higher PRS for attention-deficit/hyperactivity disorder (ADHD) and adverse developmental/mental health outcomes in childhood and adolescence was reported by five studies. Additionally, associations between PRS for bipolar disorder or major depressive disorder and adverse outcomes of interest were also described by two studies; and two studies highlighted associations between schizophrenia PRS and mental health disorders in childhood. The remaining studies highlighted shared polygenic contributions between and within NDDs and mental health disorders in children. CONCLUSION: The findings of this systematic review suggest that PRS for neurodevelopmental and mental health disorders may associate with adverse neurodevelopmental and mental health outcomes from early childhood to adolescence. In addition, these associations seemed not to be phenotype-specific, suggesting potential shared genetic variation across the phenotypes of interest.