Convergent genetic pathways linking neuropsychiatric and ocular disorders in children

Clinical and epidemiological studies conducted in children have suggested a potential link between neuropsychiatric and ocular disorders. However, the existence and directionality of this relationship remain inconsistent, likely due to the complex interplay between genetic predisposition and environmental factors that may influence both conditions.

We investigated the overall and local genetic correlations and causal relationship between eight neuropsychiatric disorders and five ocular disorders based on large-scale genome-wide association study cohorts from Psychiatric Genomics Consortium and UK Biobank. An in-house independent cohort (2,726 attention deficit hyperactivity disorder (ADHD) cases and 16,299 controls) was also assessed to confirm the disease relationships. We further performed joint analyses to pinpoint the shared genetic loci. Finally, we explored their underlying biological pathways by SNP- and Gene-based enrichment analyses.

We discovered significant positive genetic correlations between autism spectrum disorder (ASD) and myopia/astigmatism; inverse genetic correlation and potential causal relationship between ADHD and myopia/astigmatism. The aggregated protective effect of ADHD on myopia and astigmatism was demonstrated using Mendelian randomization, and was validated in the independent in-house cohort. In total, 124 loci were found to be shared between psychiatric diseases and refractive errors. Enrichment analyses highlighted early neurodevelopmental processes as key shared genetic mechanisms that may play a critical role in the development of childhood-onset neuropsychiatric disorders and refractive errors.

Our findings indicate a shared genetic architecture underlying the development of childhood-onset neuropsychiatric disorders and refractive errors. These results help clarify the clinically observed associations between ADHD, ASD, and refractive errors and provide evidence that shared early neurodevelopmental processes contribute to both conditions. Together, the findings offer a novel perspective on the neurogenetic basis of refractive error and its connection to early brain development.