One gene, SCN1A, appears twice in this page and means something different each time: a common variant that shifts risk a little, and a rare change that causes severe epilepsy in a child. Telling those two apart is most of what genetics can offer here.
A seizure is what happens when a population of neurons fires together when it should not. Epilepsy is the tendency to have them repeatedly without an obvious external cause, and it is common: roughly 50 million people live with it worldwide, and about 1 person in 100 will be diagnosed at some point.
It is not one disease. It is a category holding conditions with quite different causes — a stroke, a head injury, a brain malformation, an infection, an autoimmune process, and in a large share of cases nothing identifiable at all. Genetics matters in some of those and not in others, and the honest first sentence is that most people with epilepsy do not have a genetic explanation anybody can name.
Two completely different research programmes both produce sentences with "epilepsy" and a gene in them, and they mean different things.
Rare and powerful. A small number of children have epilepsy caused by a single change with a large effect. The best known is SCN1A: a loss-of-function change there causes Dravet syndrome, a severe epilepsy beginning in the first year of life. These are found by sequencing an affected child, they are usually new in that child rather than inherited, and finding one changes clinical decisions — including which drugs to avoid.
Common and weak. Genome-wide studies scan hundreds of thousands of people for positions that differ slightly between those with epilepsy and those without. They find real associations, and each one shifts risk by a small amount. The positions on this page come from that second kind of study.
SCN1A appears in both. The same gene carries rare changes that cause a severe childhood epilepsy, and common variants that nudge the risk of epilepsy in general. Reading a common SCN1A variant as though it meant Dravet syndrome would be a serious error, and it is the error this page exists to prevent.
The largest study behind these pages pooled genome-wide data across all epilepsies and reported associations including SCN1A, PCDH7 and a position near MMP8. A separate study of genetic generalised epilepsy reported a locus near VRK2. These are population findings. None of them is a test, none is diagnostic, and carrying any of them is entirely compatible with never having a seizure.
This is the part of the page with real consequences, and it is about medicines rather than about causes.
Nothing here should be used to start, stop or change an antiseizure medicine. Stopping one abruptly is dangerous.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 266 more positions to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Source not recorded rs121918810 (SCN1A), rs796052984 (SCN1A), rs1057518703 (SCN1A), rs794726766 (SCN1A), rs794726826 (SCN1A), rs796053029 (SCN1A), rs121917912 (SCN1A), rs121917921 (SCN1A), rs1553547380 (SCN1A), rs2468225401 (SCN1A), rs1573963975 (SCN1A), rs121917952 (SCN1A) and 235 more
International League Against Epilepsy Consortium on Complex Epilepsies 2023, Nature genetics rs60055328 (SCN1A), rs2236951 (CACNA2D2), rs13032423 (ACTG1P22), rs62151809 (near LINC01965), rs77876353 (near ACTG1P22), rs9861238 (near STAC), rs6545674 (VRK2), rs469999 (near MIR3201), rs739431 (SLC38A3), rs16955463 (SKAP1), rs4807201 (AP3D1), rs114131287 (near ACVR1B) and 2 more — PMID:37653029
Sakaue S et al. 2021, Nature genetics rs998956939 (EXT1), rs187977998 (ADGRL3) — PMID:34594039
Jang HW et al. 2015, Epilepsy research rs79007183 (CRAMP1L), rs74912790 (IFNA6) — PMID:26220383
Verma A et al. 2024, Science (New York, N.Y.) rs73151649 (near RNU7-14P) — PMID:39024449
2025-08-06 · Leveraging the enrichment analysis from a genome-wide association study against epilepsy-focusing on the role of tryptophan catabolites pathway in patients with drug-resistant epilepsy. Frontiers in Nutrition. 2025. DOI:10.3389/fnut.2025.1539145
Drug-resistant epilepsy (DRE) is a subset of epilepsy that doesn't respond to standard medication and carries elevated risk of psychiatric comorbidity and cognitive impairment. This study used Taiwan Biobank GWAS data and pathway-enrichment analysis (via the Reactome database) to identify candidate biological mechanisms, landing on the tryptophan catabolites (TRYCATs) pathway -- the route by which the amino acid tryptophan is broken down into compounds including serotonin, kynurenine and kynurenic acid. It then validated this in real patients: DRE patients had significantly lower blood levels of several TRYCATs (tryptophan, serotonin, 3-indole acetic acid, 3-indolepropionic acid, kynurenine, kynurenic acid) than controls, and changes in TRYCATs balance during 6 months of multivitamin supplementation correlated with actual seizure frequency. This is a genuine bridge from GWAS-derived pathway hypothesis to a measurable, clinically relevant biomarker, though the underlying GWAS itself did not report specific risk variants with rsIDs in a form this site could verify or link to individual pages -- the contribution here is the pathway and its clinical validation, not a named genetic locus. This site's epilepsy page carries 14 variants; this entry documents pathway-level context rather than a new variant.
How epilepsy is diagnosed. By history first — what happened, what it looked like, what came before it — supported by EEG and usually by MRI. There is no genetic test that diagnoses epilepsy, and a normal EEG does not exclude it.
When genetic testing is offered. Mainly in epilepsies beginning in infancy or early childhood, in epilepsy with developmental delay, and where a specific syndrome is suspected. Panels and exome sequencing look for rare changes with large effects. That is a different test from a consumer genotyping array, which cannot see most of them.
SCN1A specifically. It encodes part of a sodium channel. Loss-of-function changes cause Dravet syndrome and milder changes cause the GEFS+ spectrum. The clinical importance is not only the diagnosis: sodium-channel-blocking drugs can worsen seizures in Dravet syndrome, so knowing the cause changes the prescription.
Inheritance. Most epilepsy does not follow a simple pattern. Having a first-degree relative with epilepsy raises risk somewhat, and the absolute risk stays low. The rare severe forms are frequently caused by changes that arose new in the affected child, which is why they can appear in a family with no history at all.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Epilepsy comes down to these specific, well-studied positions — not a diagnosis. 280 positions are linked to this page; the ones this page's own text discusses are shown first.
SCN1A · rs60055328
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 16 of 280 linked studies with a resolved discovery ancestry.
Research-derived gene–drug associations only — not a prescription, dosing guide, or medical advice. Always follow your prescriber's guidance.
| Gene | Drug | What the research shows |
|---|---|---|
| POLG | Valproic acid and valproate | This is a contraindication rather than a dose. Valproate is one of the most useful antiseizure medicines there is, and in a person with a mitochondrial disorder caused by POLG variants it can precipitate liver failure that is often fatal. The US prescribing information carries a boxed contraindication in known POLG-related mitochondrial disease and in children under two unless such disease has been excluded, because in that age group the risk is highest and the diagnosis is often not yet made. Separately, valproate interferes with the disposal of ammonia, so in someone with a urea cycle disorder — from variants in NAGS, CPS1, OTC, ASS1 or ASL — it can cause hyperammonaemic encephalopathy, a medical emergency, and it is contraindicated there too. Neither kind of variant is found by a consumer genotyping array, and this catalogue holds no POLG variant at all. The decision belongs to the clinician treating the epilepsy, and nothing here should be used to start, stop or change a medicine. (US prescribing information for valproate sodium / divalproex sodium (boxed contraindications: POLG-related mitochondrial disease, urea cycle disorders). CPIC lists POLG–valproic acid at level A/B and the urea cycle genes at level B; no CPIC guideline has been published for either.) |
| CYP2C19 | Brivaracetam | An ordinary dosing question beside the valproate note above it. CYP2C19 is the main route by which brivaracetam is cleared, so a poor metaboliser reaches higher concentrations on the same dose and may need less of it, while an ultrarapid metaboliser reaches lower ones. CPIC lists the pair at level B, which means the evidence is worth knowing about and is not strong enough for a dosing rule — a distinction the level exists to make. Dose is set by the clinician and by how the seizures respond. (CPIC lists CYP2C19–brivaracetam at level B; no CPIC guideline has been published for the pair.) |
| CYP2C19 | Clobazam | Clobazam (Onfi), added to other treatment for Lennox-Gastaut syndrome, is turned into an active form that CYP2C19 clears. In poor metabolisers, whose CYP2C19 barely works, its US label says that form reaches about 3 to 5 times the usual level, so it starts them at 5 mg a day and raises the dose slowly to half the usual steps, considering the full maximum only from day 21. (US prescribing information for ONFI (clobazam), revised March 2024, sections 2.5 and 12.5. This is the label itself, not a CPIC guideline.) |
Databases, guidelines and references
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Epilepsy. MyGeneLog™. https://www.mygenelog.com/conditions/epilepsy
Almost certainly not on that basis. These come from studies comparing large groups, and each position shifts risk by a small amount. They are not a test, and carrying one is entirely compatible with never having a seizure.
No, and this is the most important misreading to avoid. Dravet syndrome is caused by rare changes that disable the gene, found by sequencing. A common SCN1A variant reported by a consumer array is a different kind of finding entirely and does not indicate it.
It can rule one out in a specific case. HLA-B*15:02 carriers face a substantially raised risk of severe skin reactions on carbamazepine, oxcarbazepine and phenytoin, and testing before starting is recommended where that allele is common. Beyond that, choice of medicine is clinical.
Sometimes, and rarely in a simple way. A close relative with epilepsy raises risk somewhat while the absolute risk stays low. The severe childhood forms are often caused by a change that arose new in that child, so they appear in families with no history.
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