Multivariate genetic analyses test for the presence of a general 'n' factor underlying neurodevelopmental conditions

Neurodevelopmental conditions often emerge early in life and have substantial genetic influences. There are significant genetic correlations between neurodevelopmental conditions, such as between autism spectrum disorder (Autism) and attention deficit-hyperactivity disorder (ADHD), and they are listed together in diagnostic manuals. Here we assess whether there is a single underlying genetic neurodevelopmental ('n') factor for neurodevelopmental conditions.

Genetic summary statistics of neurodevelopmental conditions, or their proxy traits, were used to model the genetic relationship between neurodevelopmental conditions. Summary statistics contain the effect sizes of each variant's association with a neurodevelopmental condition from a genome-wide association study. Single and multiple common factor models were fitted to the data using genomic structural equation modelling.

A single common factor model did not provide a good fit for the genetic architecture of neurodevelopmental conditions. A two-factor model fitted the data best. It was also found that the common genetic variation associated with a trait representing motor development, namely age at onset of walking, was negatively and positively associated with ADHD and Autism, respectively, suggesting some genetic differentiation between these two common neurodevelopmental conditions.

These results provide insight into the genetic architecture of neurodevelopmental conditions and their inter-related structure. Data on measured common genetic variation, as discovered from recent genome-wide association studies, does not support the hypothesis that all neurodevelopmental conditions fall into a single 'n' factor.