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Record W2120386191 · doi:10.1186/gm249

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

2011· article· en· W2120386191 on OpenAlexaff
Carmen Antúnez, Merçé Boada, Antonio González‐Pérez, Javier Gayán, Reposo Ramírez‐Lorca, Juan Marín, Isabel Hernández, Concha Moreno‐Rey, Francisco Jesús Morón, Jesús López‐Arrieta, Ana Mauleón, Maitée Rosende‐Roca, Fuensanta Noguera-Perea, Agustina Legaz-García, L. Vivancos, Juan Velasco, José Miguel Carrasco, Montserrat Alegret, Martirio Antequera-Torres, Salvadora Manzanares, Alejandro Romo, Irene Blanca, Susana Ruiz, Ana Espinosa, Sandra Castaño, Blanca García García, B. Martínez, Georgina Vinyes, Asunción Lafuente, James T. Becker, José Jorge Galán, Manuel Serrano‐Ríos, Enrique Vázquez, Lluís Tárraga, María Eugenia Sáez, Oscar L. López, Luís Miguel Real, Agustı́n Ruiz

Bibliographic record

VenueGenome Medicine · 2011
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsNexen (Canada)
FundersNational Institute on AgingInstituto de Salud Carlos IIIUniversity of California, San DiegoNational Institute of Biomedical Imaging and BioengineeringUniversity of California, Los AngelesGenentechNational Institutes of HealthCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas AsociadasJunta de AndalucíaEisaiNorthern California Institute for Research and EducationAlzheimer's Disease Neuroimaging InitiativeF. Hoffmann-La RocheMedpaceGlaxoSmithKlineBristol-Myers SquibbEli Lilly and CompanyAstraZenecaPfizerCorporación Tecnológica de AndalucíaElanNovartisSynarcDana FoundationAlzheimer's AssociationFoundation for the National Institutes of Health
KeywordsGenome-wide association studyOdds ratioGeneticsBiologyGenetic associationImputation (statistics)PopulationMeta-analysisSubfamilyGeneMedicineSingle-nucleotide polymorphismGenotypeInternal medicineComputer scienceMissing data

Abstract

fetched live from OpenAlex

BACKGROUND: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population. METHODS: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings. RESULTS: Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls). CONCLUSIONS: Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases.

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)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.005
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.247
Teacher spread0.221 · 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 designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations102
Published2011
Admission routes1
Has abstractyes

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