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Record W3207881611 · doi:10.1093/g3journal/jkab278

Smooth-threshold multivariate genetic prediction incorporating gene–environment interactions

2021· article· en· W3207881611 on OpenAlexfundno aff
Masao Ueki, Gen Tamiya

Bibliographic record

VenueG3 Genes Genomes Genetics · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsnot available
FundersNational Institute on AgingNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchNational Institutes of HealthGenentechIXICOJapan Society for the Promotion of Science LondonH. Lundbeck A/SServierEisaiNorthern California Institute for Research and EducationF. Hoffmann-La RocheUniversity of Southern CaliforniaPfizerBioClinicaBiogenBristol-Myers SquibbUniversity of California, San DiegoU.S. Department of DefenseMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationAlzheimer's AssociationJapan Society for the Promotion of ScienceFoundation for the National Institutes of Health
KeywordsUnivariateGenome-wide association studyMultivariate statisticsGenetic associationRegressionGene–environment interactionAdditive genetic effectsBiologyRegression analysisAdditive modelComputer scienceInteractionStatisticsComputational biologyMachine learningMathematicsGeneticsHeritabilitySingle-nucleotide polymorphismGene

Abstract

fetched live from OpenAlex

We propose a genetic prediction modeling approach for genome-wide association study (GWAS) data that can include not only marginal gene effects but also gene-environment (GxE) interaction effects-i.e., multiplicative effects of environmental factors with genes rather than merely additive effects of each. The proposed approach is a straightforward extension of our previous multiple regression-based method, STMGP (smooth-threshold multivariate genetic prediction), with the new feature being that genome-wide test statistics from a GxE interaction analysis are used to weight the corresponding variants. We develop a simple univariate regression approximation to the GxE interaction effect that allows a direct fit of the STMGP framework without modification. The sparse nature of our model automatically removes irrelevant predictors (including variants and GxE combinations), and the model is able to simultaneously incorporate multiple environmental variables. Simulation studies to evaluate the proposed method in comparison with other modeling approaches demonstrate its superior performance under the presence of GxE interaction effects. We illustrate the usefulness of our prediction model through application to real GWAS data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

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)0.003
metaresearch head score (Gemma)0.009
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.011
Threshold uncertainty score0.022

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.009
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.002
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0020.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.000

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 head0.019
GPT teacher head0.256
Teacher spread0.237 · 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 designSimulation or modeling
Domainnot available
GenreMethods

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

Citations2
Published2021
Admission routes1
Has abstractyes

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