Common genetic variants are associated with increased likelihood of latent co-occurring neurodevelopmental and mental health factors among autistic individuals.

Autistic individuals show elevated rates of co-occurring neurodevelopmental and mental health conditions, yet the genetic architecture of those comorbidities remains unclear. Using phenotypic (N = 74,204) and genetic (N = 17,582) data from the SPARK study, we investigated the factor structure, heritability, genetic correlation with autism (pleiotropy) and corresponding conditions in the general population (additivity). First, confirmatory factor analysis identified three correlated factors mirroring general population patterns: behavioural (ADHD, disruptive behaviour disorders), cothymic (depression, anxiety), and thought disorder (schizophrenia, bipolar). Second, all three factors had significant SNP heritabilities whilst rare variants were not associated with the tested factors in our sample. Third, polygenic scores and genetic correlations revealed positive shared genetics between the three factors and corresponding conditions in the general population but not with autism, supporting the additivity hypothesis. Fourth, within-family analyses (N = 5236 trios) demonstrated direct but not indirect genetic effects for the behavioural and cothymic factors. In sum, we find evidence for additive effects of other genetic factors in contributing to some latent co-occurring neurodevelopmental and mental health conditions in autism.