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Record W4400490878 · doi:10.1038/s41467-024-49998-0

Characterising the genetic architecture of changes in adiposity during adulthood using electronic health records

2024· article· en· W4400490878 on OpenAlexaff
Samvida S. Venkatesh, Habib Ganjgahi, Duncan S. Palmer, Kayesha Coley, Gregorio V. Linchangco, Qin Hui, Peter W.F. Wilson, Yuk‐Lam Ho, Kelly Cho, Kadri Arumäe, Andres Metspalu, Lili Milani, Tõnu Esko, Reedik Mägi, Mari Nelis, Georgi Hudjashov, Laura B. L. Wittemans, Christoffer Nellåker, Uku Vainik, Yan V. Sun, Chris Holmes, Cecilia M. Lindgren

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersClarendon FundEngineering and Physical Sciences Research CouncilTartu ÜlikoolEesti TeadusagentuurEuropean Regional Development FundLi Ka Shing FoundationEuropean CommissionUniversity of OxfordNIHR Oxford Biomedical Research CentreRhodes ScholarshipsNovo NordiskNational Institute for Health and Care ResearchNovo Nordisk UK Research FoundationWellcome TrustResearch Councils UKOffice of Research and DevelopmentU.S. Department of Veterans AffairsNovartis FoundationWellcomeAlan Turing InstituteEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentBill and Melinda Gates FoundationNational Institutes of HealthUniversity of LeicesterU.S. Department of Health and Human Services
KeywordsGenetic architectureBody mass indexHeritabilityBiobankObesityGenome-wide association studyDemographyGenetic correlationMedicineGerontologyGeneticsBiologySingle-nucleotide polymorphismGenetic variationQuantitative trait locusInternal medicineGenotypeGene

Abstract

fetched live from OpenAlex

Obesity is a heritable disease, characterised by excess adiposity that is measured by body mass index (BMI). While over 1,000 genetic loci are associated with BMI, less is known about the genetic contribution to adiposity trajectories over adulthood. We derive adiposity-change phenotypes from 24.5 million primary-care health records in over 740,000 individuals in the UK Biobank, Million Veteran Program USA, and Estonian Biobank, to discover and validate the genetic architecture of adiposity trajectories. Using multiple BMI measurements over time increases power to identify genetic factors affecting baseline BMI by 14%. In the largest reported genome-wide study of adiposity-change in adulthood, we identify novel associations with BMI-change at six independent loci, including rs429358 (APOE missense variant). The SNP-based heritability of BMI-change (1.98%) is 9-fold lower than that of BMI. The modest genetic correlation between BMI-change and BMI (45.2%) indicates that genetic studies of longitudinal trajectories could uncover novel biology of quantitative traits in adulthood.

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)0.007
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 score0.018
Threshold uncertainty score0.036

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.007
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.003
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.014
GPT teacher head0.311
Teacher spread0.297 · 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

Citations18
Published2024
Admission routes1
Has abstractyes

Explore more

Same venueNature Communications→Same topicGenetic Associations and Epidemiology→French-language works237,207→