MétaCan
Menu
Back to cohort
Record W4409785609 · doi:10.1162/imag_a_00580

Leveraging multimodal neuroimaging and GWAS for identifying modality-level causal pathways to Alzheimer’s disease

2025· article· en· W4409785609 on OpenAlex
Yuan Tian, Daniel Felsky, Jessica Gronsbell, Jun Young Park

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueImaging Neuroscience · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsCentre for Addiction and Mental HealthPublic Health OntarioUniversity of Toronto
FundersNational Heart, Lung, and Blood InstituteMedical Research CouncilHjartaverndAustralasian Gynaecological Endoscopy and Surgery SocietyConnaught FundSimon Fraser UniversityKrembil FoundationNatural Sciences and Engineering Research Council of CanadaAlzheimer’s Research UKInstitut National de la Santé et de la Recherche MédicaleUniversité de LilleCanadian Institutes of Health ResearchCentre hospitalier régional universitaire de LilleCentre for Addiction and Mental Health FoundationWellcome TrustDevelopment of Innovative Strategies for a Transdisciplinary approach to ALZheimer's diseaseNational Institute on AgingAlzheimer's AssociationUniversity of TorontoErasmus Medisch CentrumBundesministerium für Bildung und ForschungNational Institutes of HealthMcLaughlin Centre, University of Toronto
KeywordsNeuroimagingGenome-wide association studyDiseaseModality (human–computer interaction)PsychologyNeuroscienceImaging geneticsMedicineComputer scienceArtificial intelligenceBiologySingle-nucleotide polymorphismInternal medicineGenetics

Abstract

fetched live from OpenAlex

The UK Biobank study has produced thousands of brain imaging-derived phenotypes (IDPs) collected from more than 40,000 genotyped individuals so far, facilitating the investigation of genetic and imaging biomarkers for brain disorders. Motivated by efforts in genetics to integrate gene expression levels with genome-wide association studies (GWASs), recent methods in imaging genetics adopted an instrumental variable (IV) approach to identify causal IDPs for brain disorders. However, several methodological challenges arise with existing methods in achieving causality in imaging genetics, including horizontal pleiotropy and high dimensionality of candidate IVs. In this work, we propose testing the causality of each brain modality (i.e., structural, functional, and diffusion magnetic resonance imaging (MRI)) for each gene as a useful alternative, which offers an enhanced understanding of the roles of genetic variants and imaging features on behavior by controlling for the pleiotropic effects of IDPs from other imaging modalities. We demonstrate the utility of the proposed method by using Alzheimer's GWAS data from the UK Biobank and the International Genomics of Alzheimer's Project (IGAP) study. Our method is implemented using summary statistics, which is available on GitHub.

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 imitation

Not 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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.671
Threshold uncertainty score0.751

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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)

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 head0.079
GPT teacher head0.349
Teacher spread0.270 · 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