Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
fundA Canadian funder is recorded on the work.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.
VenuemedRxiv · 2020
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersNational Institute of Biomedical Imaging and BioengineeringNational Institute of Neurological Disorders and StrokeNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Mental HealthNational Institute on AgingCenter for Innovative MedicineInstituto de Salud Carlos IIINational Institutes of HealthAssociazione Italiana Ricerca AlzheimerUK Dementia Research InstituteMedical Research CouncilAcademy of FinlandGrifolsServierMinisterio de Economía y CompetitividadUniversity College London Hospitals NHS Foundation TrustIXICODemensfondenSahlgrenska UniversitetssjukhusetNovo NordiskVetenskapsrådetSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungStockholms Läns LandstingBanco Bilbao Vizcaya ArgentariaCanadian Institutes of Health ResearchEuropean CommissionKnut och Alice Wallenbergs StiftelseFundación Salud 2000Université de LilleKarolinska InstitutetJuho Vainion SäätiöMinisterstvo Zdravotnictví Ceské RepublikyFonds Wetenschappelijk OnderzoekNational Health and Medical Research CouncilSuomen KulttuurirahastoUniverzita Karlova v PrazeGeneralitat de CatalunyaBundesministerium für Bildung und ForschungAXA Research FundMinistero della SaluteH. Lundbeck A/SInstitut National de la Santé et de la Recherche MédicaleUniversität HeidelbergVlaamse regeringNational Institute for Health and Care ResearchCardiff UniversityNational Research FoundationUniversity of NottinghamGenentechFondation pour la Recherche sur AlzheimerSocialdepartementetBioClinicaNewcastle UniversityUniversitat de BarcelonaKing's College LondonUniversity of CambridgeNovartis Pharmaceuticals CorporationMotor Neurone Disease AssociationNational Institute for Social Care and Health ResearchUniversiteit AntwerpenMinisterstvo Školství, Mládeže a TělovýchovyHigher Education Funding Council for WalesDipartimenti di EccellenzaUniversity of California, San DiegoAlzheimer's SocietyCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseSorbonne UniversitéNorthern California Institute for Research and EducationSouth London and Maudsley NHS Foundation TrustLudwig Boltzmann GesellschaftEuropean Regional Development FundAlzheimer's Research TrustU.S. Department of DefenseHersenstichtingBrightFocus FoundationEli Lilly and CompanyNorth Bristol NHS TrustItä-Suomen YliopistoFundação para a Ciência e a TecnologiaEU Joint Programme – Neurodegenerative Disease ResearchPfizerWellcome TrustAgence Nationale de la RechercheBiogenEisaiUniversity of Southern CaliforniaFoundation for the National Institutes of HealthMinistero dell’Istruzione, dell’Università e della RicercaFundación BBVAF. Hoffmann-La RocheSeinäjoen KeskussairaalaVanderbilt UniversityMeso Scale DiagnosticsYrjö Jahnssonin SäätiöU.S. Department of Veterans AffairsConsortium canadien en neurodégénérescence associée au vieillissementBristol-Myers SquibbSigrid Juséliuksen SäätiöStichting MS ResearchUniversity of SouthamptonEconomic and Social Research CouncilOffice of Research and DevelopmentStichting ALS NederlandAlzheimer's Association
KeywordsDementiaDiseaseAlzheimer's diseaseFrontotemporal dementiaGenome-wide association studyNeuroscienceBioinformaticsBiologyMedicineGeneGeneticsInternal medicineSingle-nucleotide polymorphismGenotype
Abstract
fetched live from OpenAlexABSTRACT Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, and the failure to find effective treatments suggests that the underlying pathology remains poorly understood. Due to its strong heritability, deciphering the genetic landscape of AD and related dementia (ADD) is a unique opportunity to advance our knowledge. We completed a meta-analysis of genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases and 401,577 controls) with the most promising signals followed-up in 25,392 independent AD cases and 276,086 controls. We report 75 risk loci for ADD, including 42 novel ones. Pathway-enrichment analyses confirm the involvement of amyloid/Tau pathways, highlight the role of microglia and its potential interaction with APP metabolism. Numerous genes exhibited differential expression or splicing in AD-related conditions and gene prioritization implies EGFR signaling and TNF-α pathway through LUBAC complex. We also generated a novel polygenic risk score strongly associated with the risk of future dementia or progression from mild cognitive impairment to dementia. In conclusion, by more than doubling the number of loci associated with ADD risk, our study offers new insights into the pathophysiological processes underlying AD and offers additional therapeutic entry-points and tools for translational genomics.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.482
Threshold uncertainty score0.623
Codex and Gemma teacher scores by category
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Teacher spread0.236 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
