Evidence map›Paper›PMID 31608925›Full record

ArticleBrain : a journal of neurology2019

Polygenic burden in focal and generalized epilepsies.

Costin Leu, Remi Stevelink, Alexander W Smith, Slavina B Goleva, Masahiro Kanai, Lisa Ferguson, Ciaran Campbell, Yoichiro Kamatani, Yukinori Okada, Sanjay M Sisodiya and 11 more

Erratum issuedOpen access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 2 pooled it
11.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Genetic Diagnosis in Epilepsy: Implications for Clinical Management.Current neurology and neuroscience reports · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
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  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Women With Genetic Epilepsies.Neurology. Genetics · 2025
    Review

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 9 institutions in 7 countries.

Costin LeuGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Remi StevelinkDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Alexander W SmithStanley Center for Psychiatric Research, Broad Institute of Harvard and M.I.T, Cambridge, MA, USA.
Slavina B GolevaDivision of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Masahiro KanaiStanley Center for Psychiatric Research, Broad Institute of Harvard and M.I.T, Cambridge, MA, USA.
Lisa FergusonEpilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Ciaran CampbellDepartment of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Yoichiro KamataniLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Yukinori OkadaLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Sanjay M SisodiyaDepartment of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London, UK.
Gianpiero L CavalleriDepartment of Molecular and Cellular Therapeutics, The Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Bobby P C KoelemanDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Holger LercheDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Lara JehiEpilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Lea K DavisDivision of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Imad M NajmEpilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Aarno PalotieStanley Center for Psychiatric Research, Broad Institute of Harvard and M.I.T, Cambridge, MA, USA.
Mark J DalyStanley Center for Psychiatric Research, Broad Institute of Harvard and M.I.T, Cambridge, MA, USA.
Robyn M BuschEpilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Epi25 Consortium
Dennis LalGenomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Broad Institute · USCleveland Clinic · USRoyal College of Surgeons in Ireland · IEUniversity Medical Center Utrecht · NLVanderbilt University · USHertie Institute for Clinical Brain Research · DEKyoto University · JPNational Hospital for Neurology and Neurosurgery · GBRIKEN Center for Integrative Medical Sciences · JP

Funding

Center for Common Disease GeneticsUM1HG008895 · NHGRI · BROAD INSTITUTE, INC. · PI DALY, MARK JOSEPH, GABRIEL, STACEY · 2016 to 2020
$111.2M
Epi25 Clinical Phenotyping R03R03NS108145 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2018 to 2019
$137k
Department of Health 09/144/09Medical Research Council G0800637Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHGRI NIH HHS UM1 HG008895NINDS NIH HHS R03 NS108145
6 · The paper itself

Abstract

Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japanese-ancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64×10-15; Cleveland: P = 2.85×10-4; Finnish-ancestry Epi25: P = 1.80×10-4) or population controls (Epi25: P = 2.35×10-70; Cleveland: P = 1.43×10-7; Finnish-ancestry Epi25: P = 3.11×10-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99×10-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74×10-19; Cleveland: P = 1.69×10-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60×10-15; Cleveland: P = 1.39×10-2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls-in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment.

Indexed as

Cohort StudiesCost of IllnessDatabases, FactualEpilepsies, PartialEpilepsy, GeneralizedFemaleGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansMaleMultifactorial InheritancePolymorphism, Single NucleotideWhite Peoplecommon variant riskepilepsygenetic generalized epilepsygenetics

Identifiers

PMID31608925
PMCPMC6821205
OpenAlexW2980424458

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.