ArticleScience translational medicine2016
Quantifying prion disease penetrance using large population control cohorts.
Open access · greenAbstract read
In one paragraph
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
219citing papers in PubMed, 2 pooled it
33.1field-weighted citation impact, top 1% of its field
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Who cites it
219 citing papers in PubMed, 2 syntheses or guidelines pooled it, 463 citations in OpenAlex.
- Systematic Review of Clinical and Pathophysiological Features of Genetic Creutzfeldt-Jakob Disease Caused by a Val-to-Ile Mutation at Codon 180 in the Prion Protein Gene.International journal of molecular sciences · 2022Pooled it
- Evidence for penetrance in patients without a family history of disease: a systematic review.European journal of human genetics : EJHG · 2020Pooled it
- Mortality of Individuals WithNeurology. Genetics · 2026Article
- Life at the interface: Byron Caughey's search for prion disease inhibitors through chemistry, structure, and cell physiology.Acta neuropathologica · 2026Review
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.PLoS pathogens · 2026Article
- Variant Site-Specific Natural History of Titin-Induced Cardiomyopathy: An International Multicenter Registry.Circulation. Genomic and precision medicine · 2026Article
- Depleting prion protein using splice-switching small molecules.bioRxiv : the preprint server for biology · 2026Article
- Generation of Infectious Prions Amenable to Site-Specific Click Chemistry.ACS chemical biology · 2026Article
- Comprehensive Characterization of 98 Chinese Cases of Genetic Creutzfeldt-Jakob Disease With T188K Mutation.Annals of clinical and translational neurology · 2026Article
- PrP turnover in vivo and the time to effect of prion disease therapeutics.PLoS pathogens · 2026Article
- Divalent siRNA for prion disease.Nucleic acids research · 2026Article
- A self-complementary recombinant adeno-associated virus vector coding for an anchorless prion protein carrying the G127V mutation extends survival in a rodent prion disease model.bioRxiv : the preprint server for biology · 2026Article
- Divalent siRNA for prion disease.bioRxiv : the preprint server for biology · 2026Article
- Limited transmission of V180I genetic Creutzfeldt-Jakob disease in knock-in mice models.The Journal of general virology · 2026Article
- High Proportions of GAP43 Positivity in the Cerebrospinal Fluids of Patients with Sporadic and Certain Types of Genetic Creutzfeldt-Jakob Diseases by Western Blot Analysis.International journal of molecular sciences · 2026Article
- Review
- The Risk of Transmission of Genetic Prion Diseases is Greater Than 50.European journal of neurology · 2025Article
- Exploring penetrance of clinically relevant variants in over 800,000 humans from the Genome Aggregation Database.Nature communications · 2025Article
- Structure and Dynamics of the Misfolding Intermediate in the Pathogenic T183A Prion Protein Mutant.Journal of chemical theory and computation · 2025Article
- Mortality of individuals with antemortem genetic testing formedRxiv : the preprint server for health sciences · 2025Article
159 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
64 authors at 16 institutions in 6 countries.
Eric Vallabh MinikelProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA. Prion Alliance, Cambridge, MA 02139, USA. eminikel@broadinstitute.org macarthur@atgu.mgh.harvard.edu.
Sonia M VallabhProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA. Prion Alliance, Cambridge, MA 02139, USA.
Monkol LekProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Karol EstradaProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Kaitlin E SamochaProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
J Fah SathirapongsasutiResearch, 23andMe Inc., Mountain View, CA 94041, USA.
Cory Y McLeanResearch, 23andMe Inc., Mountain View, CA 94041, USA.
Joyce Y TungResearch, 23andMe Inc., Mountain View, CA 94041, USA.
Linda P C YuResearch, 23andMe Inc., Mountain View, CA 94041, USA.
Pierluigi GambettiNational Prion Disease Pathology Surveillance Center, Cleveland, OH 44106, USA.
Janis BlevinsNational Prion Disease Pathology Surveillance Center, Cleveland, OH 44106, USA.
Shulin ZhangUniversity Hospitals Case Medical Center, Cleveland, OH 44106, USA.
Yvonne CohenNational Prion Disease Pathology Surveillance Center, Cleveland, OH 44106, USA.
Wei ChenNational Prion Disease Pathology Surveillance Center, Cleveland, OH 44106, USA.
Masahito YamadaDepartment of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan.
Tsuyoshi HamaguchiDepartment of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8640, Japan.
Nobuo SanjoDepartment of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Hidehiro MizusawaNational Center Hospital, National Center of Neurology and Psychiatry, Tokyo 187-8551, Japan.
Yosikazu NakamuraDepartment of Public Health, Jichi Medical University, Shimotsuke 329-0498, Japan.
Tetsuyuki KitamotoDepartment of Neurological Science, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Steven J CollinsAustralian National Creutzfeldt-Jakob Disease Registry, The University of Melbourne, Parkville, Victoria 3010, Australia.
Alison BoydAustralian National Creutzfeldt-Jakob Disease Registry, The University of Melbourne, Parkville, Victoria 3010, Australia.
Robert G WillNational Creutzfeldt-Jakob Disease Research & Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
Richard KnightNational Creutzfeldt-Jakob Disease Research & Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
Claudia PontoNational Reference Center for the Surveillance of Human Transmissible Spongiform Encephalopathies, Georg-August-University, Goettingen 37073, Germany.
Inga ZerrNational Reference Center for the Surveillance of Human Transmissible Spongiform Encephalopathies, Georg-August-University, Goettingen 37073, Germany.
Theo F J KrausCenter for Neuropathology and Prion Research (ZNP), Ludwig-Maximilians-University, Munich 81377, Germany.
Sabina EigenbrodCenter for Neuropathology and Prion Research (ZNP), Ludwig-Maximilians-University, Munich 81377, Germany.
Armin GieseCenter for Neuropathology and Prion Research (ZNP), Ludwig-Maximilians-University, Munich 81377, Germany.
Miguel CaleroCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid 28031, Spain.
Jesús de Pedro-CuestaCentro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid 28031, Spain.
Stéphane HaïkINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, Pierre and Marie Curie University Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Epinière, 75013 Paris, France. Assistance Publique-Hôpitaux de Paris (AP-HP), Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
Jean-Louis LaplancheAP-HP, Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, 75010 Paris, France.
Elodie Bouaziz-AmarAP-HP, Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, 75010 Paris, France.
Jean-Philippe BrandelINSERM U 1127, CNRS UMR 7225, Sorbonne Universités, Pierre and Marie Curie University Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Epinière, 75013 Paris, France. Assistance Publique-Hôpitaux de Paris (AP-HP), Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, F-75013 Paris, France.
Sabina CapellariIstituto di Ricovero e Cura a Carattere Scientifico, Institute of Neurological Sciences, Bologna 40123, Italy. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna 40126, Italy.
Piero ParchiIstituto di Ricovero e Cura a Carattere Scientifico, Institute of Neurological Sciences, Bologna 40123, Italy. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna 40126, Italy.
Anna PoleggiDepartment of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome 00161, Italy.
Anna LadoganaDepartment of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome 00161, Italy.
Anne H O'Donnell-LuriaProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA.
Konrad J KarczewskiProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Jamie L MarshallProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Markku LaaksoDepartment of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio 70210, Finland.
Karen L MohlkeDepartment of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Anna KählerKarolinska Institutet, Stockholm SE-171 77, Sweden.
Kimberly ChambertStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Steven McCarrollStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Patrick F SullivanDepartment of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Karolinska Institutet, Stockholm SE-171 77, Sweden.
Christina M HultmanKarolinska Institutet, Stockholm SE-171 77, Sweden.
Shaun M PurcellIcahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Pamela SklarIcahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Sven J van der LeeDepartment of Epidemiology, Erasmus Medical Center (MC), Rotterdam 3000 CA, Netherlands.
Annemieke RozemullerDutch Surveillance Centre for Prion Diseases, Department of Pathology, University Medical Center, Utrecht 3584 CX, Netherlands.
Casper JansenDutch Surveillance Centre for Prion Diseases, Department of Pathology, University Medical Center, Utrecht 3584 CX, Netherlands.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center (MC), Rotterdam 3000 CA, Netherlands.
Robert KraaijDepartment of Internal Medicine, Erasmus MC, Rotterdam 3000 CA, Netherlands.
Jeroen G J van RooijDepartment of Internal Medicine, Erasmus MC, Rotterdam 3000 CA, Netherlands.
M Arfan IkramDepartment of Epidemiology, Erasmus Medical Center (MC), Rotterdam 3000 CA, Netherlands.
André G UitterlindenDepartment of Epidemiology, Erasmus Medical Center (MC), Rotterdam 3000 CA, Netherlands. Department of Internal Medicine, Erasmus MC, Rotterdam 3000 CA, Netherlands.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus Medical Center (MC), Rotterdam 3000 CA, Netherlands.
Exome Aggregation Consortium (ExAC)
Mark J DalyProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniel G MacArthurProgram in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA 02142, USA. Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA. eminikel@broadinstitute.org macarthur@atgu.mgh.harvard.edu.
Massachusetts General Hospital · USHarvard University · USKarolinska Institutet · SEBroad Institute · USIcahn School of Medicine at Mount Sinai · USIstituto Superiore di Sanità · ITKanazawa University · JPUniversity of Bologna · ITUniversity of Melbourne · AUJichi Medical University · JPKuopio University Hospital · FITohoku University · JPTokyo Medical and Dental University · JPUniversity Hospitals Case Medical Center · USUniversity of Michigan–Ann Arbor · USUniversity of North Carolina at Chapel Hill · US
Funding
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Scott Soleimanpour · 2013 to 2026
$24.3MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MTargeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3MComputational resources for genomic interpretation of type 2 diabetesU54DK105566 · NIDDK · BROAD INSTITUTE, INC. · PI MACARTHUR, DANIEL G, NEALE, BENJAMIN MICHAEL · 2014 to 2017
$8.6MGenetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2M2/2 Large-Scale Genetic Studies of Schizophrenia in SwedenR01MH095034 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI STAHL, ELI A · 2012 to 2019
$3.6MDEV. OF NEW DIAGNOSTIC METHODS/RESEARCH PROG. TO DET.THE IEHSE.UR8CI515004 · CI · CASE WESTERN RESERVE UNIVERSITY · PI GAMBETTI, PIERLUIGI · 1997 to 2006
$3.1MAnnotation and interpretation of loss-of-function polymorphisms in human genomesR01GM104371 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI MACARTHUR, DANIEL G · 2013 to 2016
$1.3MThe Human Knockout Project: systematic discovery of loss-of-function variants in humansF32GM115208 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI KARCZEWSKI, KONRAD · 2015 to 2016
$109kDepartment of HealthNCPDCID CDC HHS UR8 CI515004NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK093757NIDDK NIH HHS U01 DK062370NIDDK NIH HHS U54 DK105566NIDDK NIH HHS U54DK105566NIGMS NIH HHS F32 GM115208NIGMS NIH HHS R01 GM104371NIGMS NIH HHS R01GM104371NIMH NIH HHS R01 MH095034PHS HHS UR8/CCU515004
Abstract
More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1 to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression.
Indexed as
PenetranceCase-Control StudiesCohort StudiesGenetic Predisposition to DiseaseHumansMutationPrion DiseasesPrionsRisk FactorsPrions
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