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Record W4410695240 · doi:10.1002/alz.70237

Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset

2025· article· en· W4410695240 on OpenAlexfundno aff
Yuk Yee Leung, Wan‐Ping Lee, Amanda Kuzma, Heather Nicaretta, Otto Valladares, Prabhakaran Gangadharan, Liming Qu, Yi Zhao, Youli Ren, Po‐Liang Cheng, Pavel P. Kuksa, Hui Wang, Heather White, Živadin Katanić, Lauren Bass, Naveen Saravanan, Emily Greenfest‐Allen, Maureen Kirsch, Laura B. Cantwell, Taha Iqbal, Nicholas R. Wheeler, John Farrell, Congcong Zhu, Tamil Iniyan Gunasekaran, Pedro Mena, Yumi Jin, Luke Carter, Xiaoling Zhang, Badri N. Vardarajan, Arthur W. Toga, Michael L. Cuccaro, Timothy J. Hohman, William S. Bush, Adam C. Naj, Eden R. Martin, Clifton L. Dalgard, Brian W. Kunkle, Lindsay A. Farrer, Richard Mayeux, Jonathan L. Haines, Margaret A. Pericak‐Vance, Gerard D. Schellenberg, Li‐San Wang

Bibliographic record

VenueAlzheimer s & Dementia · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenomics and Rare Diseases
Canadian institutionsnot available
FundersReta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology,University College LondonNational Center for Research ResourcesNational Institute of Environmental Health SciencesNational Institute of Biomedical Imaging and BioengineeringNational Human Genome Research InstituteNational Institute on Drug AbuseNational Heart, Lung, and Blood InstituteNational Institute on AgingMedical Research CouncilCanadian Institutes of Health ResearchTau ConsortiumUniformed Services University of the Health SciencesVictorian Brain BankUniversity of PennsylvaniaAustrian Science FundMedizinische Universität GrazH. Lundbeck A/SNational Institute of Neurological Disorders and StrokeDeutsches Zentrum für Neurodegenerative ErkrankungenAlzheimer's Drug Discovery FoundationNational Institutes of HealthÖsterreichische ForschungsförderungsgesellschaftOesterreichische NationalbankUniversity of TorontoSociale en Geesteswetenschappen, NWONederlandse Organisatie voor Wetenschappelijk OnderzoekEuropean CommissionGenentechErasmus Medisch CentrumBaylor College of MedicineDepartment of Internal Medicine, University of UtahEU Joint Programme – Neurodegenerative Disease ResearchGE HealthcareEuropean Research CouncilNorthern California Institute for Research and EducationNovartis Pharmaceuticals CorporationU.S. Department of Health and Human ServicesMayo ClinicFujirebio USArizona Department of Health ServicesAlzheimer's AssociationBiogenUniversity of MiamiCurePSPBioClinicaAlzheimer's Disease Neuroimaging InitiativeEli Lilly and CompanyWellcome TrustUniversity of Southern CaliforniaMerckMinistry of EducationFramingham Heart StudyTakeda Pharmaceutical CompanyCase Western Reserve UniversityRainwater Charitable FoundationGHR FoundationAbbVie
KeywordsLinkage disequilibriumGeneticsGenomeWhole genome sequencingReference genomeBiologyDNA sequencingGenetic architecture1000 Genomes ProjectComputational biologyGenome-wide association studyGenomicsGenetic associationAllelePhenotypeSingle-nucleotide polymorphismHaplotypeGenotypeGene

Abstract

fetched live from OpenAlex

INTRODUCTION: The Alzheimer's Disease Sequencing Project (ADSP) is a national initiative to understand the genetic architecture of Alzheimer's disease and related dementias (ADRD) by integrating whole genome sequencing (WGS) with other genetic, phenotypic, and harmonized datasets from diverse populations. METHODS: The Genome Center for Alzheimer's Disease (GCAD) uniformly processed WGS from 36,361 ADSP samples, including 35,014 genetically unique participants of which 45% are from non-European ancestry, across 17 cohorts in 14 countries in this fourth release (R4). RESULTS: This sequencing effort identified 387 million bi-allelic variants, 42 million short insertions/deletions, and 6.8 million structural variants. Annotations and quality control data are available for all variants and samples. Additionally, detailed phenotypes from 15,927 participants across 10 domains are also provided. A linkage disequilibrium panel was created using unrelated AD cases and controls. DISCUSSION: Researchers can access and analyze the genetic data via the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) Data Sharing Service, the VariXam, or NIAGADS GenomicsDB. HIGHLIGHTS: We detailed the genetic architecture and quality of the Alzheimer's Disease Sequencing Project release 4 whole genome sequences. We identified 435 million single nucleotide polymorphisms, insertions and deletions, and structural variants from diverse genomes. We harmonized extensive phenotypes, linkage disequilibrium reference panel on subset of samples. Data is publicly available at NIAGADS Data Storage Site, variants and annotations are browsable on two different websites.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.010
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Dataset · Consensus signal: Dataset
Teacher disagreement score0.029
Threshold uncertainty score0.097

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.010
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0030.007
Science and technology studies0.0020.000
Scholarly communication0.0020.001
Open science0.0030.002
Research integrity0.0020.002
Insufficient payload (model declined to judge)0.0290.026

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.

Opus teacher head0.026
GPT teacher head0.280
Teacher spread0.254 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreDataset

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations23
Published2025
Admission routes1
Has abstractyes

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