We collected 977 genes, including gene clusters, associated with epilepsy from the expert-compiled list from Wang et al. (2017)10. These genes were manually curated and examined from multiple genetic databases and represent genes are directly related to epilepsy, or indirectly lead to epilepsy through influence on the central nervous system or other systems; the subgroups of epilepsy genes are defined in Table Table1.1. These 977 epilepsy-associated genes were mapped to 999 genes in the multiplex network. The number of genes increased because gene clusters were separated into individual genes. We also collected 913 autism-associated genes from the Simons Foundation Autism Research Initiative (SFARI) Gene (access date: January 5, 2020), a community-driven knowledgebase of autism spectrum disorder60. SFARI Gene has the evidence and the strength of the genetic association for each gene; subgroups of autism genes are defined in Table Table1.1. These 913 autism-associated genes were also mapped to the multiplex network. In total there were 1707 epilepsy- and autism-associated genes.

In additional analyses, we also used the most updated whole-exome sequencing (WES) data we could find for each of autism and epilepsy in order to test whether our results were also applicable to a less biased gene set38,61. The 102 autism genes with FDR <  = 0.1 from the autism WES study (see Table S2 in Satterstrom et al., 2020) were used as the autism gene set. The top 200 most significant epilepsy genes outputted by the gene burden test from the epilepsy WES study (see Table S17 in Feng et al., 2019) were used as the epilepsy gene set.

The gene lists for schizophrenia, bipolar disorder, and intellectual disability were retrieved from a paper by Wang et al. (2018)62. The schizophrenia gene list originally comes from the SZgene63 database and a GWAS study64. The bipolar disorder gene list originally comes from the BDgene database65. The intellectual disability gene list originally comes from BrainSpan and are documented in a previous publication by the same authors66.

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