Evidence map›Paper›PMID 40731221›Full record

ArticleEBioMedicine2025

SUDEP risk is influenced by longevity genomics: a polygenic risk score study.

Helena Martins, James D Mills, Susanna Pagni, Medine I Gulcebi, Angeliki Vakrinou, Patrick B Moloney, Lisa M Clayton, Ravishankara Bellampalli, Hannah Stamberger, Sarah Weckhuysen and 17 more

Abstract read
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In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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

27 authors.

Helena MartinsUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK.
James D MillsUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK; Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands.
Susanna PagniUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK.
Medine I GulcebiUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK; Department of Medical Pharmacology, Marmara University School of Medicine, Istanbul, Turkey.
Angeliki VakrinouUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK.
Patrick B MoloneyUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK.
Lisa M ClaytonUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK.
Ravishankara BellampalliUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK.
Hannah StambergerApplied & Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Translational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
Sarah WeckhuysenApplied & Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Translational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium; Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
Pasquale StrianoIRCCS G. Gaslini, Pediatric Neurology and Muscular Diseases Unit, Full Member of ERN-EPICARE, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy.
Federico ZaraUOC Genetica Medica, IRCCS Istituto, Giannina Gaslini, Genoa, Italy.
Richard D BagnallMolecular Cardiology Group at Centenary Institute, The University of Sydney, Sydney, New South Wales, 2050, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 2050, Australia.
Rebekah V HarrisEpilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, 3084, Australia.
Kate M LawrenceEpilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, 3084, Australia.
Lynette G SadleirDepartment of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.
Douglas E CromptonEpilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, 3084, Australia; Department of Neurology, Northern Health, Epping, Victoria, Australia.
Daniel FriedmanDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, 10016, United States.
Juliana LazeDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, 10016, United States.
Ling LiDepartment of Pediatrics, University of Maryland School of Medicine, MD, 21223, United States; Office of the Chief Medical Examiner (OCME), Baltimore, MD, 21201, United States.
Samuel F BerkovicEpilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, 3084, Australia.
Christopher SemsarianMolecular Cardiology Group at Centenary Institute, The University of Sydney, Sydney, New South Wales, 2050, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 2050, Australia.
Ingrid E SchefferEpilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, 3084, Australia; Florey and Murdoch Children's Research Institutes, Victoria, 3052, Australia; Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria, 3052, Australia.
Orrin DevinskyDepartment of Neurology, NYU Grossman School of Medicine, New York, NY, 10016, United States.
Karoline KuchenbaeckerUniversity College London Division of Psychiatry, Maple House, London, W1T 7BN, UK.
Simona BalestriniUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK; Department of Neuroscience and Medical Genetics, Meyer Children's Hospital IRCSS, University of Florence, 50139, Florence, Italy.
Sanjay M SisodiyaUniversity College London Queen Square Institute of Neurology, London, WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, SL9 0RJ, UK. Electronic address: s.sisodiya@ucl.ac.uk.

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundSudden Unexpected Death in Epilepsy (SUDEP) is a rare and tragic outcome in epilepsy, identified by those with the condition as their most serious concern. Although several clinical factors are associated with elevated SUDEP risk, mechanisms underlying SUDEP are poorly understood, making individual risk prediction challenging, especially early in the disease course. We hypothesised that common genetic variation contributes to SUDEP risk.

methodsGenetic data from people who had succumbed to SUDEP was compared to data from people with epilepsy who had not succumbed to SUDEP and from healthy controls. Polygenic risk scores (PRSs) for longevity, intelligence and epilepsy were compared across cohorts. Reactome pathways and gene ontology terms implicated by the contributing single nucleotide polymorphisms (SNPs) were explored. In the subset of SUDEP cases with the necessary data available, a risk score was calculated using an existing risk prediction tool (SUDEP-3); the added value to this prediction of SNP-based genomic information was evaluated.

findingsOnly European-ancestry participants were included. 161 SUDEP cases were compared to 768 cases with epilepsy and 1153 healthy controls. PRS for longevity was significantly reduced in SUDEP cases compared to disease (P = 0·0096) and healthy controls (P = 0·0016), as was PRS for intelligence (SUDEP cases compared to disease (P = 0·0073) and healthy controls (P = 0·00024)). The PRS for epilepsy did not differ between SUDEP cases and disease controls (P = 0·76). SNP-determined pathway and gene ontology analysis highlighted those related to inter-neuronal communication as amongst the most enriched in SUDEP. Addition of PRS for longevity and intelligence to SUDEP-3 scores improved risk prediction in a subset of cases (38) and controls (703), raising the area-under-the-curve in a receiver-operator characteristic from 0·699 using SUDEP-3 alone to 0·913 when PRSs were added.

interpretationCommon genetic variation contributes to SUDEP risk, offering new approaches to improve risk prediction and to understand underlying mechanisms.

fundingThe Amelia Roberts Fund; CURE Epilepsy; Epilepsy Society, UK; Finding A Cure for Epilepsy and Seizures (FACES).

Indexed as

EpilepsyGenetic Predisposition to DiseaseGenomicsLongevityMultifactorial InheritanceSudden Unexpected Death in EpilepsyAdultAgedCase-Control StudiesFemaleGenetic Risk ScoreHumansMaleMiddle AgedPolymorphism, Single NucleotideRisk FactorsDeathEpilepsyIntelligenceLongevityRisk

Identifiers

PMID40731221
PMCPMC12368338

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.