Abstract
Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia. We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences. We found that ADHD PGS were associated with earlier walking age (β = -0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment. Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.
Highlights
Children’s timely attainment of developmental milestones is an important indicator of the extent to which early neurodevelopment is progressing typically (Bishop, Thurm, Farmer, & Lord, 2016; Johnson, Gliga, Jones, & Charman, 2015; Mayes & Calhoun, 2003)
Autism shares some features with attention deficit hyperactivity disorder (ADHD), another childhoodonset neurodevelopmental condition, but ADHD is typically diagnosed in mid-childhood or later (Kessler et al, 2007)
In the motor development analyses (Fig. 1; top panel), we found robust evidence that ADHD polygenic scores (PGS) is associated with younger age at first walking (β = −0.033, Bonferroni-adjusted p < 0.001) an association that was present in both males and females
Summary
Children’s timely attainment of developmental milestones is an important indicator of the extent to which early neurodevelopment is progressing typically (Bishop, Thurm, Farmer, & Lord, 2016; Johnson, Gliga, Jones, & Charman, 2015; Mayes & Calhoun, 2003). Schizophrenia, typically not diagnosed until early adulthood (Jones, 2013), is increasingly conceptualised as a neurodevelopmental disorder (Lewis & Levitt, 2002) This conceptualisation is supported both by evidence of some clinical overlap with disorders such as autism and ADHD (De Crescenzo et al, 2019), and by associations between delays in the attainment of early developmental milestones and later schizophrenia diagnoses (Filatova et al, 2017; Isohanni et al, 2001; Sørensen et al, 2010; Stochl et al, 2019). We investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Associations are small but robust and, in the case of autism PGS, differentiated by sex These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population
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