The Alzheimer's Disease Sequencing Project: Study design and sample selection
Notice bibliographique
Résumé
Late-onset Alzheimer disease (LOAD) is the leading cause of dementia worldwide, with substantial economic and public health implications.1 LOAD is a neurodegenerative disease characterized by progressive dementia typically manifesting in the seventh to ninth decades. Neuropathological changes precede clinical symptoms by 10–20 years, resulting in clinically asymptomatic individuals carrying neuropathologic features of LOAD.2 Much of the heritability of LOAD remains unexplained, despite LOAD having a high heritability (60%–80%) and despite the identification of the APOE locus, a major genetic determinant for LOAD.3 Genetic analyses have identified more than 25 other variants associated with smaller individual effects on disease risk.4 Acknowledgment: The Alzheimer's Disease Sequencing Project (ADSP) comprises 2 Alzheimer's Disease (AD) genetics consortia and 3 National Human Genome Research Institute (NHGRI)-funded Large Scale Sequencing and Analysis Centers (LSAC). The 2 AD genetics consortia are the Alzheimer's Disease Genetics Consortium (ADGC) funded by the NIA (U01 AG032984), and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) funded by the NIA (R01 AG033193), the National Heart, Lung, and Blood Institute (NHLBI), other NIH institutes, and other foreign governmental and nongovernmental organizations. The Discovery Phase analysis of sequence data is supported through UF1AG047133 (to G. Schellenberg, L.A. Farrer, M.A. Pericak-Vance, R. Mayeux, and J.L. Haines); U01AG049505 to S. Seshadri; U01AG049506 to E. Boerwinkle; U01AG049507 to E. Wijsman; and U01AG049508 to A. Goate. Data generation and harmonization in the Follow-up Phases is supported by U54AG052427 (to G. Schellenberg and Wang). The ADGC cohorts include Adult Changes in Thought (ACT), the Alzheimer's Disease Centers (ADC), the Chicago Health and Aging Project (CHAP), the Memory and Aging Project (MAP), Mayo Clinic (MAYO), Mayo Parkinson's Disease controls, the University of Miami, the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study (MIRAGE), the National Cell Repository for Alzheimer's Disease (NCRAD), the National Institute on Aging Late Onset Alzheimer's Disease Family Study (NIA-LOAD), the Religious Orders Study (ROS), the Texas Alzheimer's Research and Care Consortium (TARC), Vanderbilt University/Case Western Reserve University (VAN/CWRU), the Washington Heights-Inwood Columbia Aging Project (WHICAP) and the Washington University Sequencing Project (WUSP), the Columbia University Hispanic–Estudio Familiar de Influencia Genetica de Alzheimer (EFIGA), the University of Toronto (UT), and Genetic Differences (GD). The CHARGE cohorts with funding provided by 5RC2HL102419 and HL105756, include the following: the Atherosclerosis Risk in Communities (ARIC) Study which is conducted as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), the Austrian Stroke Prevention Study (ASPS), the Cardiovascular Health Study (CHS), the Erasmus Rucphen Family Study (ERF), the Framingham Heart Study (FHS), and the Rotterdam Study (RS). The 3 LSACs are the Human Genome Sequencing Center at the Baylor College of Medicine (U54 HG003273), the Broad Institute Genome Center (U54HG003067), and the Washington University Genome Institute (U54HG003079). Biological samples and associated phenotypic data used in primary data analyses were stored at Study Investigators institutions and at the National Cell Repository for Alzheimer's Disease (NCRAD, U24AG021886) at Indiana University funded by the NIA. Associated Phenotypic Data used in primary and secondary data analyses were provided by Study Investigators, the NIA-funded Alzheimer's Disease Centers (ADCs), and the National Alzheimer's Coordinating Center (NACC, U01AG016976) and the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS, U24AG041689) at the University of Pennsylvania, funded by the NIA and at the Database for Genotypes and Phenotypes (dbGaP) funded by the NIH. This research was supported in part by the Intramural Research Program of the NIH and the National Library of Medicine. Contributors to the Genetic Analysis Data included Study Investigators on projects that were individually funded by the NIA and other NIH institutes, and by private U.S. organizations, or foreign governmental or nongovernmental organizations.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,017 | 0,018 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,002 |
| Méta-épidémiologie (sens large) | 0,003 | 0,001 |
| Bibliométrie | 0,002 | 0,003 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,009 | 0,003 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».