Early manifestations of genetic risk for neurodevelopmental disorders

Background Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism), and schizophrenia, are highly heritable neurodevelopmental disorders, affecting the lives of many individuals. To improve prevention and treatment, it is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls.Method Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a sub-sample of 15 205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother-reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18 months, 3, 5 and 8 years. Linear regression models in a multi-group framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, and sex was used as a grouping variable. Results Before the age of 2, PRS associations were found with language difficulties, inattention and hyperactivity, mostly increasing in strength up to 8 years. PRS for autism was associated with motor difficulties as early as 6 months. By 8 years, all measured neurodevelopmental traits had shown some association with at least one neurodevelopmental PRS. In general, genetic risk manifested similarly in boys and girls. Associations were, however, stronger in girls for language difficulties and ADHD PRS at 8 years. The association between schizophrenia PRS and inattention was found in girls only at 18 months. For autism PRS, associations with social communication difficulties at 18 months, and motor difficulties at 5 years were observed in boys only. Conclusions Genetic risk for neurodevelopmental disorders manifests early in childhood and broadly across behavioral measures of neurodevelopment. Manifestations may be sex specific in some domains, but these findings need to be replicated.