1. Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.
- Author
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Hegemann L, Corfield EC, Askelund AD, Allegrini AG, Askeland RB, Ronald A, Ask H, St Pourcain B, Andreassen OA, Hannigan LJ, and Havdahl A
- Subjects
- Humans, Norway, Female, Male, Child, Preschool, Cohort Studies, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders diagnosis, Mothers, Autistic Disorder genetics, Genetic Predisposition to Disease, Adult, Fathers, Genome-Wide Association Study, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit Disorder with Hyperactivity diagnosis, Schizophrenia genetics, Genetic Heterogeneity, Phenotype
- Abstract
Background: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations., Methods: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests., Results: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items r
g range = - 0.27-0.78), ADHD (items rg range = - 0.40-1), and schizophrenia (items rg range = - 0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other., Conclusions: 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 and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs., (© 2024. The Author(s).)- Published
- 2024
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