ArticleThe Lancet. Neurology2020
Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.
Open access · greenAbstract read
In one paragraph
Article in The Lancet. Neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
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.
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.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The First Meta-Analysis of the M129V Single-Nucleotide Polymorphism (SNP) of the Prion Protein Gene (Cells · 2021Pooled it
- Accurate genomic predictions for chronic wasting disease in North American elk.G3 (Bethesda, Md.) · 2026Article
- The protein disulfide isomerase P4HB/PDIA1 modulates cellular and misfolded forms of the prion protein.PLoS pathogens · 2026Article
- Cross-Omic Comparative Analysis Identifies Transcriptomic Signatures and Exploratory Gene Set-Level Signals in Sporadic Creutzfeldt-Jakob Disease.International journal of molecular sciences · 2026Article
- Sporadic Creutzfeldt-Jakob disease: a multidimensional review from epidemiology to treatment and prognosis.Journal of neurology · 2026Review
- Modification of early behavioural, physiological and neuropathological endpoints by syntaxin-6 knockout in a humanised P301S transgenic model of tauopathy.Acta neuropathologica · 2026Article
- Cross-disease genetic and epigenetic architecture of thebioRxiv : the preprint server for biology · 2026Article
- Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.medRxiv : the preprint server for health sciences · 2026Article
- Intracellular trafficking SNARE protein, syntaxin-6, modifies prion cellular phenotypes and risk of disease development in vivo.Acta neuropathologica · 2025Article
- Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.Brain : a journal of neurology · 2025Article
- Search for a genetic cause of variably protease-sensitive prionopathy.PLoS pathogens · 2025Article
- Exploring the Relationship Between Sporadic Creutzfeldt-Jakob Disease and Gut Microbiota Through a Mendelian Randomization Study.Molecular neurobiology · 2025Article
- Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes.Nature biomedical engineering · 2025Article
- Human Genetic Evidence for New Targets in Prion Diseases: Opportunities and Challenges.Sub-cellular biochemistry · 2025Review
- Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer's disease.Nature communications · 2024Article
- Article
- Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.Acta neuropathologica · 2024Article
- Neuropathologically-directed profiling ofbioRxiv : the preprint server for biology · 2024Article
- Gerstmann-Sträussler-Scheinker Disease Presenting as Late-Onset Slowly Progressive Spinocerebellar Ataxia, and Comparative Case Series with Neuropathology.Movement disorders clinical practice · 2024Article
- Creutzfeldt-Jakob disease and other prion diseases.Nature reviews. Disease primers · 2024Review
Corrections and comments
- Commented on by
Authors and funding
65 authors at 20 institutions in 13 countries.
Emma JonesMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Holger HummerichMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Emmanuelle ViréMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
James UphillMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Athanasios DimitriadisMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Helen SpeedyMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Tracy CampbellMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Penny NorsworthyMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Liam QuinnMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Jerome WhitfieldMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Jacqueline LinehanMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Zane JaunmuktaneDivision of Neuropathology, University College London Hospitals National Health Service Foundation Trust, London, UK; Department of Clinical and Movement Neurosciences and Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, London, UK.
Sebastian BrandnerDivision of Neuropathology, University College London Hospitals National Health Service Foundation Trust, London, UK; Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Parmjit JatMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Akin NihatMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK; National Prion Clinic, University College London Hospitals National Health Service Foundation Trust, London, UK.
Tze How MokMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK; National Prion Clinic, University College London Hospitals National Health Service Foundation Trust, London, UK.
Parvin AhmedMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK.
Steven CollinsAustralian National Creutzfeldt-Jakob Disease Registry, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
Christiane StehmannAustralian National Creutzfeldt-Jakob Disease Registry, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
Shannon SarrosAustralian National Creutzfeldt-Jakob Disease Registry, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.
Gabor G KovacsInstitute of Neurology, Medical University of Vienna, Vienna, Austria; Department of Laboratory Medicine and Pathobiology and Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada; Laboratory Medicine Program, Krembil Brain Institute, University Health Network, Toronto, ON, Canada.
Michael D GeschwindUniversity of California San Francisco Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Aili GolubjatnikovUniversity of California San Francisco Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA.
Karl FrontzekInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Herbert BudkaInstitute of Neuropathology, University of Zurich, Zurich, Switzerland; Medical University Vienna, Vienna, Austria.
Adriano AguzziInstitute of Neuropathology, University of Zurich, Zurich, Switzerland.
Hata Karamujić-ČomićDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands.
Sven J van der LeeDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands.
Carla A Ibrahim-VerbaasDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Beata SikorskaDepartment of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Ewa GolanskaDepartment of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Pawel P LiberskiDepartment of Molecular Pathology and Neuropathology, Medical University of Lodz, Lodz, Poland.
Miguel CaleroChronic Disease Programme (UFIEC-CROSADIS) and Network Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), and Alzheimer Disease Research Unit, CIEN Foundation, Queen Sofia Foundation Alzheimer Centre, Instituto de Salud Carlos III, Madrid, Spain.
Olga CaleroChronic Disease Programme (UFIEC-CROSADIS) and Network Centre for Biomedical Research in Neurodegenerative Diseases (CIBERNED), and Alzheimer Disease Research Unit, CIEN Foundation, Queen Sofia Foundation Alzheimer Centre, Instituto de Salud Carlos III, Madrid, Spain.
Pascual Sanchez-JuanNeurology Service, University Hospital Marqués de Valdecilla, University of Cantabria, CIBERNED and IDIVAL, Santander, Spain.
Antonio SalasUnidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia, Spain.
Federico Martinón-TorresTranslational Paediatrics and Infectious Diseases, Department of Paediatrics, Hospital Clínico Universitario de Santiago de Compostela, Galicia, Spain.
Elodie Bouaziz-AmarDepartment of Biochemistry and Molecular Biology, Lariboisière Hospital, AP-HP, University of Paris, Paris, France.
Stéphane HaïkSorbonne Université, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France; Cellule nationale de référence des maladies de Creutzfeldt-Jakob, AP-HP, University Hospital Pitié-Salpêtrière, Paris, France.
Jean-Louis LaplancheDepartment of Biochemistry and Molecular Biology, Lariboisière Hospital, AP-HP, University of Paris, Paris, France.
Jean-Phillipe BrandelSorbonne Université, INSERM U1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, Paris, France; Cellule nationale de référence des maladies de Creutzfeldt-Jakob, AP-HP, University Hospital Pitié-Salpêtrière, Paris, France.
Phillipe AmouyelINSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE, Labex DISTALZ, University of Lille, Lille, France.
Jean-Charles LambertINSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE, Labex DISTALZ, University of Lille, Lille, France.
Piero ParchiIRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy.
Anna Bartoletti-StellaIRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Sabina CapellariIRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Anna PoleggiDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Anna LadoganaDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Maurizio PocchiariDepartment of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Serena AneliDepartment of Medical Sciences, Università degli studi di Torino, Torino, Italy.
Giuseppe MatulloDepartment of Medical Sciences, Università degli studi di Torino, Torino, Italy.
Richard KnightNational Creutzfeldt-Jakob Disease Research and Surveillance Unit, Edinburgh, UK.
Saima ZafarDepartment of Neurology, Clinical Dementia Centre and National Reference Centre for Creutzfeldt-Jakob Disease Surveillance, University Medical School, Göttingen, Germany; German Centre for Neurodegenerative Diseases (DZNE), Göttingen, Germany; Biomedical Engineering and Sciences Department, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad, Pakistan.
Inga ZerrDepartment of Neurology, Clinical Dementia Centre and National Reference Centre for Creutzfeldt-Jakob Disease Surveillance, University Medical School, Göttingen, Germany; German Centre for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Stephanie BoothPrion Disease Program, Public Health Agency of Canada, Winnipeg, MB, Canada.
Michael B CoulthartCanadian Creutzfeldt-Jakob Disease Surveillance System, Public Health Agency of Canada, Ottawa, ON, Canada.
Gerard H JansenDepartment of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada.
Katie GlisicDepartments of Pathology and Neurology, Case Western Reserve University, Cleveland, OH, USA; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA.
Janis BlevinsDepartments of Pathology and Neurology, Case Western Reserve University, Cleveland, OH, USA; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA.
Pierluigi GambettiDepartments of Pathology and Neurology, Case Western Reserve University, Cleveland, OH, USA; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA.
Jiri SafarDepartments of Pathology and Neurology, Case Western Reserve University, Cleveland, OH, USA; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA.
Brian ApplebyDepartments of Pathology and Neurology, Case Western Reserve University, Cleveland, OH, USA; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA.
John CollingeMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK; National Prion Clinic, University College London Hospitals National Health Service Foundation Trust, London, UK.
Simon MeadMedical Research Council Prion Unit, University College London Institute of Prion Diseases, London, UK; National Prion Clinic, University College London Hospitals National Health Service Foundation Trust, London, UK. Electronic address: s.mead@prion.ucl.ac.uk.
Medical Research Council · GBUniversity College London · GBCase Western Reserve University · USErasmus University Rotterdam · NLIstituto Superiore di Sanità · ITMedical University of Lodz · PLMRC Prion Unit · GBUniversity of Zurich · CHFlorey Institute of Neuroscience and Mental Health · AUGerman Center for Neurodegenerative Diseases · DEIstituto delle Scienze Neurologiche di Bologna · ITNational Hospital for Neurology and Neurosurgery · GBPublic Health Agency of Canada · CAUniversity of Turin · ITAssistance Publique – Hôpitaux de Paris · FRBiomedical Research Networking Center on Neurodegenerative Diseases · ESCancer Research UK · GBCentre National de la Recherche Scientifique · FRComplejo Hospitalario Universitario de Santiago · ESFundacion Centro De Investigacion De Enfermedades Neurologicas · ES
Funding
Predicting progression of human prion diseaseR01AG031189 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GESCHWIND, MICHAEL D · 2008 to 2017
$5.7MTracking longitudinal change in presymptomatic genetic prion disease (TLC-Pre-gPrD)R01AG062562 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GESCHWIND, MICHAEL D · 2019 to 2023
$5.4MReplication mechanism of human prionsR01NS103848 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI SAFAR, JIRI G., SUREWICZ, WITOLD K · 2018 to 2022
$2.6MMedical Research Council G0400713Medical Research Council MC_U123160651Medical Research Council MC_U123160657Medical Research Council MC_UU_00024/1Medical Research Council MC_UU_00024/2Medical Research Council MC_UU_00024/9NIA NIH HHS R01 AG031189NIA NIH HHS R01 AG062562NINDS NIH HHS R01 NS103848Wellcome Trust
Abstract
backgroundHuman prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.
methodsWe did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country.
findingsSamples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10
interpretationWe present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders.
fundingMedical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.
Indexed as
Creutzfeldt-Jakob SyndromeGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRisk Factors
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
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.