GENE CONNECTIVITY ANALYSIS OF CO-EXPRESSION NETWORKS PROVIDES INSIGHTS INTO THE OMNIGENIC MODEL AND IDENTIFIES NOVEL GENETIC HUBS OF SCHIZOPHRENIA RISK

The omnigenic model posits that genetic risk for a heritable disease arises from cumulative effects of many peripheral genes on “core genes” that mechanistically drive disease traits. A relevant viewpoint to observe the implications of the omnigenic model is offered by co-expression networks. Within a co-expressed gene set, the most central genes are best poised to connect to all genes, including potential core genes, as long as genetic risk converges into the gene set. We thus evaluated the relationship between genome wide association study (GWAS) statistics and gene-set connectivity to interrogate omnigenic architecture in schizophrenia (SCZ) and other disorders.