The Seizure?Associated Genes Across Species (SAGAS) database offers insights into epilepsy genes, pathways and treatments

AbstractObjective

Decades of genetic studies on people with many different epilepsies, and on many non-human species, using many different technologies, have generated a huge body of literature about the genes associated with seizures/epilepsy. Collating this data can help uncover epilepsy genes, pathways and treatments that would otherwise be overlooked. We aimed to collate and structure these data into a database, and use the database to identify novel epilepsy genes and pathways, and to prioritise promising treatments.

Methods

We collated all the genes associated with all types of seizures/epilepsy in all species, and quantified the supporting evidence for each gene, by manually screening ~10,000 publications, and by extracting data from existing databases.

Results

The largest published dataset of epilepsy genes includes only 977 genes, whereas our database (www.sagas.ac) includes 2876 genes, which demonstrates that the number of genes that can potentially contribute to seizures/epilepsy is much higher than previously envisaged. We use our database to identify 12 hitherto unreported polygenic epilepsy genes, and 479 high-confidence monogenic epilepsy genes, and 394 more biological pathways than identified using the previous largest epilepsy genes dataset. We use a unique feature of SAGAS—the number of citations for each gene—to demonstrate that a drug is more likely to affect seizures if there is more evidence that the genes it affects are associated with seizures, and we use these data to identify promising candidate antiseizure drugs.

Significance

This database offers insights into the causes of epilepsy and its treatments, and can accelerate future epilepsy research.