Evidence map›Paper›PMID 34018700›Full record

ArticleAnnals of clinical and translational neurology2021

Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy.

Stefan Wolking, Claudia Moreau, Mark McCormack, Roland Krause, Martin Krenn, EpiPGx Consortium, Samuel Berkovic, Gianpiero L Cavalleri, Norman Delanty, Chantal Depondt and 15 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Assessment of burden and segregation profiles of CNVs in patients with epilepsy.Annals of clinical and translational neurology · 2022
    Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 17 institutions in 10 countries.

Stefan WolkingUniversité de Montréal, Montreal, Canada.ORCID 0000-0002-1460-6623
Claudia MoreauCentre Intersectoriel en Santé Durable, Université du Québec à Chicoutimi, Saguenay, Canada.
Mark McCormackMolecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.ORCID 0000-0002-8213-6141
Roland KrauseLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.ORCID 0000-0001-9938-7126
Martin KrennDepartment of Neurology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0003-3026-3082
EpiPGx Consortium
Samuel BerkovicDepartment of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Melbourne, Australia.ORCID 0000-0003-4580-841X
Gianpiero L CavalleriDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Norman DelantyDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Chantal DepondtDepartment of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Michael R JohnsonDivision of Brain Sciences, Imperial College Faculty of Medicine, London, UK.
Bobby P C KoelemanDepartment of Genetics, University Medical Center Utrecht, Utrecht, Netherlands.
Wolfram S KunzInstitute of Experimental Epileptology and Cognition Research and Department of Epileptology, University of Bonn, Bonn, Germany.
Holger LercheNeurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Anthony G MarsonDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Terence J O'BrienDepartments of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.
Slave PetrovskiCentre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Josemir W SanderDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Graeme J SillsSchool of Life Sciences, University of Glasgow, Glasgow, UK.
Pasquale StrianoPediatric Neurology and Muscular Diseases Unit, IRCCS "G. Gaslini" Institute, Genova, Italy.
Federico ZaraDepartment of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genova, Italy.
Fritz ZimprichDepartment of Neurology, Medical University of Vienna, Vienna, Austria.
Sanjay M SisodiyaDepartment of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.
Simon L GirardCentre Intersectoriel en Santé Durable, Université du Québec à Chicoutimi, Saguenay, Canada.
Patrick CossetteUniversité de Montréal, Montreal, Canada.
Royal College of Surgeons in Ireland · IEHertie Institute for Clinical Brain Research · DEIstituto Giannina Gaslini · ITMedical University of Vienna · ATNational Hospital for Neurology and Neurosurgery · GBUniversité du Québec à Chicoutimi · CAAstraZeneca (United Kingdom) · GBImperial College London · GBThe Royal Melbourne Hospital · AUThe University of Melbourne · AUUniversité de Montréal · CAUniversité Libre de Bruxelles · BEUniversity Medical Center Utrecht · NLUniversity of Bonn · DEUniversity of Glasgow · GBUniversity of Liverpool · GBUniversity of Luxembourg · LU

Funding

Medical Research Council MR/S02638X/1
6 · The paper itself

Abstract

objectiveResistance to antiseizure medications (ASMs) is one of the major concerns in the treatment of epilepsy. Despite the increasing number of ASMs available, the proportion of individuals with drug-resistant epilepsy remains unchanged. In this study, we aimed to investigate the role of rare genetic variants in ASM resistance.

methodsWe performed exome sequencing of 1,128 individuals with non-familial non-acquired focal epilepsy (NAFE) (762 non-responders, 366 responders) and were provided with 1,734 healthy controls. We undertook replication in a cohort of 350 individuals with NAFE (165 non-responders, 185 responders). We performed gene-based and gene-set-based kernel association tests to investigate potential enrichment of rare variants in relation to drug response status and to risk for NAFE.

resultsWe found no gene or gene set that reached genome-wide significance. Yet, we identified several prospective candidate genes - among them DEPDC5, which showed a potential association with resistance to ASMs. We found some evidence for an enrichment of truncating variants in dominant familial NAFE genes in our cohort of non-familial NAFE and in association with drug-resistant NAFE.

interpretationOur study identifies potential candidate genes for ASM resistance. Our results corroborate the role of rare variants for non-familial NAFE and imply their involvement in drug-resistant epilepsy. Future large-scale genetic research studies are needed to substantiate these findings.

Indexed as

Cohort StudiesDrug Resistant EpilepsyExome SequencingFemaleGenetic Association StudiesGenetic VariationHumansMalePolymorphism, Single Nucleotide

Identifiers

PMID34018700
PMCPMC8283173
OpenAlexW3163763263

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.