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. 2021 Sep 24;72:103588. doi: 10.1016/j.ebiom.2021.103588

Table 1.

Gene-sets investigated in this study. The number of gene-sets in each category is given in parenthesis.

Group of all protein coding genes (1):
-all genes annotated by snpEff as protein coding.
Groups based on brain expression (34): Expression in the brain, regional, cellular and sub-cellular expression patterns.
Brain-expressed LOF-intolerant genes:
excluding genes with no expression in the cortex/hippocampus
-pLI > 0.995.
-pLI 0.9-0.995.
-pLI 0.8-0.9.
Brain-expressed missense-intolerant genes:
excluding genes with no expression in the cortex/hippocampus
-Z-score > 3.09.
-Z-score 2.5-3.09.
-Z-score 2-2.5.		 Cortical and hippocampal expression level:
-High, Moderate, Low in the cortex.
-High, Moderate, Low in the hippocampus.
Brain development:
-Brain development genes
(Gene-Ontology group).
-Brain developmental genes (extended group).
-Early developmental genes.
-Late developmental genes.
Enrichment in the brain:
-Brain-enriched -Brain-enhanced.		 Cell-type-specific enrichment:
-Neurons -glial cells
-Excitatory neurons -Inhibitory neurons -Astrocytes -Microglia
-Oligodendrocytes -Endothelium.
Neuronal Localization:
-Axon Initial Segment.
-Synaptic (curated group).
-Synaptic (extended group).
-Synaptic vesicle and active zone.
-Pre-synaptic.
-Post-synaptic.
-Pre-synaptic only.
-Post-synaptic only.
Functional gene-sets (28): Ion channels, transporters, synaptic cycles, pathways and neurotransmitter cycles.
Ion channels, neurotransmitter receptors and related genes:
-Voltage-gated ion channels.
-Voltage-gated cation channels.
-Brain-specific voltage-gated ion channels.
-GABAA receptors.
-GABAergic pathway.
-Excitatory receptors.
-NMDAR & ARC interactors.
-PSD-95 interactors.
GABAergic/Glutamatergic synapses (GO groups):
-GABAergic synapse -Glutamatergic synapse
-only in GABAergic -only in glutamatergic
-shared genes.		 GABAergic/Glutamatergic pathways (KEGG database):
-GABAergic pathway -Glutamatergic pathway
-only in GABAergic -only in glutamatergic
-shared genes.
Additional neuronal pathways (KEGG):
-Cholinergic pathway.
-Dopaminergic pathway.
-mTOR pathway.
-Synaptic vesicle cycle.
Glutamate release, uptake and clearance cycle.		 GABA/glutamate cycles (Reactome database; pooled from multiple groups):
-GABA release, receptor activation, and clearance -
Additional neuronal groups (Reactome database):
-Presynaptic depolarization.
-Neurexins and Neuroligins.
-Synaptic Adhesion molecules.
-Receptor-type Protein Tyrosine Phosphatases.
Disease-associated and intolerant genes (14): Genes and gene-sets with known associations with epilepsy and related neurological diseases
Monogenic disease-causing genes:
-Generalized epilepsy genes.
-Focal epilepsy genes.
-Dominant epilepsy genes
-DEE genes.
-NDD with epilepsy genes.
-FMRP targets.
-MGI seizure genes.		 Top-ranking 100 genes in ILAE2 GWAS:
-Generalized epilepsy GWAS.
-Focal epilepsy GWAS.
-All epilepsies GWAS.
Brain co-expression module:
-Co-expressed module identified in non-diseased post-mortem brain tissues.
(enriched for de novo variants in DEE).		 Regulatory and co-expression modules in epilepsy:
-Co-expression network identified in brain tissues of Temporal Lobe Epilepsy patients
- Two modules within this network.
Control groups (15):
Genes not expressed in the brain:
-RNA not detected in cortex, in hippocampus, or all GTEx regions.
-Protein is depleted in the brain.		 KEGG metabolic pathways:
-Type II Diabetes.
-Carbohydrate Absorption & Digestion.
-Protein Absorption & Digestion.
-Fat Absorption & Digestion.		 KEGG cancer pathways:
- CA Breast, CA Lung, CA Colon, CA Prostate, Renal Cell Ca, CA Pancreas, Hepatocellular Ca.