Subclinical Neuropsychiatric Trait Variation in Parents of Children with Autism Spectrum Disorder: a Cohort Study

Many neuropsychiatric conditions share overlapping features underpinned by shared genetics. In this study, we examined the co-aggregation of sub-threshold variation in neuropsychiatric phenotypes in biological parents of autistic children to provide insights into the intergenerational transmission of genetic liability for autism. Autistic, neuropsychiatric (i.e., anxiety, depression, ADHD), and cognitive traits were characterized in biological parents of children enrolled in a longitudinal developmental study: 189 families of autistic children and 100 families with no autistic children were included. Families were further characterized as having only one (simplex) or more than one (multiplex) autistic child. Maternal and paternal traits were compared across groups using analysis of variance. Between-parent and within-parent correlations across trait domains examined patterns of familial trait aggregation and assessed shared versus unique contributions to the inheritance of autism. Logistic regression assessed the predictive utility of parental traits for simplex vs. multiplex group membership. Mean levels of paternal autistic traits (F(2, 224) = 5.67, FDR-adjusted p-value (q) = 0.013) and maternal anxious (F(2, 262) = 11.14, q < 0.001) and depressive (F(2, 262) = 7.08, q = 0.005) traits differed between groups. Post-hoc tests revealed elevated autistic traits in multiplex fathers (q = 0.009) and elevated anxious (q < 0.001) and depressive (q = 0.004) traits in multiplex mothers compared to parents of non-autistic children; simplex parents did not differ from either of the other groups. Parental traits jointly accounted for 7.9