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Record W4223509630 · doi:10.1038/s42003-022-03248-5

Identification of genetic effects underlying type 2 diabetes in South Asian and European populations

2022· review· en· W4223509630 on OpenAlexafffund
Marie Loh, Weihua Zhang, Hong Kiat Ng, Katharina Schmid, Amel Lamri, Tong Lin, Meraj Ahmad, Jung‐Jin Lee, Maggie C. Y. Ng, Lauren E. Petty, Cassandra N. Spracklen, Fumihiko Takeuchi, Md. Tariqul Islam, Farzana Jasmine, Anuradhani Kasturiratne, Muhammad G. Kibriya, Karen L. Mohlke, Guillaume Paré, Gauri Prasad, Hasan Shahriar, Miao Ling Chee, H Janaka de Silva, James C. Engert, Hertzel C. Gerstein, K. Radha Mani, Charumathi Sabanayagam, Marijana Vujković, Rajitha Wickremasinghe, Tien Yin Wong, Chittaranjan S. Yajnik, Salim Yusuf, Habibul Ahsan, Dwaipayan Bharadwaj, Sonia S. Anand, Michael Boehnke, Donald W. Bowden, Giriraj R. Chandak, Ching‐Yu Cheng, Norihiro Kato, Anubha Mahajan, Xueling Sim, Mark I. McCarthy, Andrew P. Morris, Jaspal S. Kooner, Danish Saleheen, John C. Chambers

Bibliographic record

VenueCommunications Biology · 2022
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsImpactMcGill UniversityHamilton Health SciencesMcMaster UniversityPopulation Health Research Institute
FundersNational Institute of Environmental Health SciencesNational Heart, Lung, and Blood InstituteBiomedical Research CouncilNational Medical Research CouncilMedical Research CouncilFogarty International CenterCanadian Institutes of Health ResearchHorizon 2020 Framework ProgrammeMRC-PHE Centre for Environment and HealthServierNational Center for Global Health and MedicineDepartment of Science and Technology, Ministry of Science and Technology, IndiaNational Institute of Neurological Disorders and StrokeUniversity of CambridgeBritish Heart FoundationNational Institute on AgingNational Institute for Health and Care ResearchEuropean CommissionJawaharlal Nehru UniversityCouncil of Scientific and Industrial Research, IndiaImperial College Healthcare NHS TrustWellcome TrustNational Institutes of HealthRegeneron PharmaceuticalsGenentechNational Institute for Health Research Health Protection Research UnitPfizerHeart and Stroke Foundation of CanadaGlaxoSmithKlineImperial College LondonAmerican Heart AssociationEli Lilly and CompanyBristol-Myers SquibbAstraZenecaNational Institute of Diabetes and Digestive and Kidney DiseasesSanofi
KeywordsType 2 diabetesQuartileGenetic associationBiologyGenome-wide association studyGeneIdentification (biology)GeneticsComputational biologyEvolutionary biologyBioinformaticsGenotypeDiabetes mellitusSingle-nucleotide polymorphismMedicineInternal medicineEndocrinology

Abstract

fetched live from OpenAlex

Abstract South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases ( n = 16,677) and controls ( n = 33,856), followed by combined analyses with Europeans (n eff = 231,420). We identify 21 novel genetic loci for significant association with T2D ( P = 4.7 × 10 −8 to 5.2 × 10 −12 ), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B , PDHB , LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.

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)0.002
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: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.003
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

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 head0.119
GPT teacher head0.379
Teacher spread0.260 · 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
GenreReview

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

Citations62
Published2022
Admission routes2
Has abstractyes

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