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Record W4415026712 · doi:10.1038/s41467-025-64927-5

The effect of type 2 diabetes genetic predisposition on non-cardiovascular comorbidities

2025· article· en· W4415026712 on OpenAlexaff
Ana Luiza Arruda, Ozvan Bocher, Henry J. Taylor, Davis Cammann, Satoshi Yoshiji, Xianyong Yin, Chi Zhao, Jingchun Chen, Alexis C. Wood, Ken Suzuki, Josep M. Mercader, Cassandra N. Spracklen, James B. Meigs, Marijana Vujković, George Davey Smith, Jerome I. Rotter, Benjamin F. Voight, Andrew P. Morris, Eleftheria Zeggini

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill UniversityMcGill Genome Centre
FundersNational Center for Advancing Translational SciencesNational Human Genome Research InstituteNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteManchester Biomedical Research CentreEuropean CommissionNational Institute for Health and Care ResearchNational Institutes of HealthAmerican Diabetes Association
KeywordsGenetic predispositionMendelian randomizationType 2 diabetesDiabetes mellitusGenetic associationGenome-wide association studyGenetic variationGenetic model

Abstract

fetched live from OpenAlex

Type 2 diabetes is associated with a range of non-cardiovascular non-oncologic comorbidities. To move beyond associations and evaluate causal effects between type 2 diabetes genetic predisposition and 21 comorbidities, we apply Mendelian randomization analysis using genome-wide association studies across multiple genetic ancestries. Additionally, leveraging eight mechanistic clusters of type 2 diabetes genetic profiles, each representing distinct biological pathways, we investigate causal links between cluster-stratified type 2 diabetes genetic predisposition and comorbidity risk. We identify causal effects of type 2 diabetes genetic predisposition driven by distinct genetic clusters. For example, the risk-increasing effects of type 2 diabetes genetic predisposition on cataracts and erectile dysfunction are primarily attributed to adiposity and glucose regulation mechanisms, respectively. We observe opposing effect directions across different genetic ancestries for depression, asthma and chronic obstructive pulmonary disease. Our findings leverage the heterogeneity underpinning type 2 diabetes genetic predisposition to prioritize biological mechanisms underlying causal relationships with comorbidities.

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)0.002
metaresearch head score (Gemma)0.008
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 score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.008
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.002
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.000

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 head0.006
GPT teacher head0.270
Teacher spread0.265 · 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

Citations5
Published2025
Admission routes1
Has abstractyes

Explore more

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