Polygenic Risk Scores for Developmental Disorders, Neuromotor Functioning During Infancy, and Autistic Traits in Childhood

Abstract

BACKGROUND: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. METHODS: In a population-based cohort in The Netherlands (2002-2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9-20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. RESULTS: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism-based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p , .001). CONCLUSIONS: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.

Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders

“…36,51−64 Further, female participants with clinical diagnoses of anxiety and depression were found to have higher ADHD PRSs than male participants, 52 while male, but not female, participants with higher ADHD PRSs had higher autistic trait scores. 56 Genetic Relationship Matrix Restricted Maximum Likelihood and Linkage Disequilibrium Score Regression. As with the PRS analyses, childhood cross-trait analyses using GREML and LDSC generally focused on ADHD and ASD, with reported genetic correlations of up to 0.37 based on clinical samples (Figure 3, Table S4, available online).…”

Prenatal maternal infection and risk for autism in offspring: A meta‐analysis

“…The relevant interactions might be with one or more rare genetic variants with a demonstrated association with autism (Buxbaum, 2009). Alternatively, they might be with the presence of multiple common variants (as indicated using polygenic risk scores) that are comparatively rare in combination (Serdarevic et al, 2020). If certain genetic vulnerabilities can be identified, then we might expect the effect of maternal infection, conditional on these vulnerabilities, to be substantially greater than what we uncovered in our meta‐analysis.…”

Gene-Environment Pathways to Cognitive Intelligence and Psychotic-Like Experiences in Children

“…The literature shows that the GPSs of cognitive performance and educational attainment are significantly associated with general intelligence 14,15 and brain development 14,16 . In addition, the GPSs of schizophrenia and ADHD successfully predicted psychiatric disorders [17][18][19] . However, the combined causal effects of genes and the neighborhood environment during development in children remain unclear.…”