Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study

Abstract

AbstractDifferent neurodevelopmental conditions such as autism and ADHD frequently co-occur. Overlapping traits and shared genetic liability are potential explanations. We examine this using data from the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), leveraging item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41 708 – 58 630). We identified 11 latent factors at the phenotypic level using maternal reports on 76 items assessing children’s motor skills, language, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. These factors showed associations with diagnoses of neurodevelopmental conditions and most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (itemrgrange = -0.27 – 0.78), ADHD (itemrgrange = -0.40 – 1), and/or schizophrenia (itemrgrange = -0.24 – 0.34). Based on patterns of item-level genetic covariance and genomic factor analyses, we find little evidence of common genetic liability across all neurodevelopmental traits. These results more so support genetic factors across more specific areas of neurodevelopment, some of which, such as prosocial behavior overlap with factors found in the phenotypic analyses. Other areas such as motor development seemed to have more heterogenous etiology, with indicators in this domain showing a less consistent pattern of genetic correlations with each other. Overall, these exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits, which in turn could have implications for clinical screening tools and programs.