The Genetics of Educational Attainment, Autism, and Schizophrenia Show Points of Convergence

Background:  Different studies have identified a link between educational attainment and psychiatric conditions like schizophrenia and autism. Biologically, this relationship can be construed in terms of two different but not necessarily mutually exclusive hypothesis: Genes for educational attainment (edu genes) are more frequently mutated in conditions like schizophrenia and autism, or genes for educational attainment interact with downstream risk pathways for autism and schizophrenia.

Objectives:  Here, we investigate both the hypothesis using summary data available from large genome-wide association studies and transcriptome studies.

Methods:  We examine the relationship between genes robustly associated with edu genes and genes and pathways implicated in autism and schizophrenia. We use genes previously identified for educational attainment using DEPICT, thereby restricting our analysis to Single Nucleotide Polymorphisms (SNPs) with P < 1x10^-5. We investigate if these genes are signficantly enriched in transcriptional modules for schizophrenia, autism, and general cognition.

Results:  We show that edu genes are highly intolerant to loss of function and are enriched in a gene-coexpression module for cognition. We identify that genes for educational attainment are more frequently mutated in autism and developmental disorders than expected by chance. We also find evidence for enrichment of edu genes in a module dysregulated in schizophrenia.

Conclusions:  In conclusion, our results highlight a role for edu genes in both upstream and downstream hypotheses.