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Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers

2013· review· en· 178 citations· W2122066039 on OpenAlex· 10.1007/s11682-013-9262-z

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

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.

Full frame distilled prediction

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.

Candidate categories
none
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Other designConsensus signal: none
Genre
Candidate signal: ReviewConsensus signal: Review
Teacher disagreement score
0.938
Threshold uncertainty score
0.883
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.056
GPT teacher head0.395
Teacher spread
0.339 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

The Genetics Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer's disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development.

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.

The record

Venue
Brain Imaging and Behavior
Topic
Alzheimer's disease research and treatments
Field
Medicine
Canadian institutions
not available
Funders
National Human Genome Research InstituteNational Institute of Mental HealthNational Institute on AgingAvid RadiopharmaceuticalsNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchUniversity of California, Los AngelesGenentechNational Institutes of HealthU.S. National Library of MedicineNational Institute of Neurological Disorders and StrokeIXICOServierEisaiBayer HealthCareH. Lundbeck A/SSunovionNovartis Pharmaceuticals CorporationDanoneGlaxoSmithKlineWashington University in St. LouisSanofiSynarcHarvard UniversityNational Center for Research ResourcesF. Hoffmann-La RocheNational Institute on Drug AbuseUniversity of PennsylvaniaBioClinicaPfizerBiogenMassachusetts General HospitalMedpaceBrigham and Women's HospitalEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentAlzheimer's Drug Discovery FoundationAstraZenecaU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbAlzheimer's Disease Neuroimaging InitiativeNational Center for Advancing Translational SciencesCure Alzheimer's FundMeso Scale DiagnosticsAlzheimer's AssociationFoundation for the National Institutes of HealthAmgen
Keywords
Genome-wide association studyAlzheimer's Disease Neuroimaging InitiativeNeuroimagingEndophenotypeBiomarkerComputational biologyImaging geneticsApolipoprotein EGenetic associationPhenotypeBiologyNeuroscienceDiseasePsychologyCognitionGeneticsGenotypeMedicineCognitive impairmentGeneSingle-nucleotide polymorphismInternal medicine
Has abstract in OpenAlex
yes