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Record W2883622734 · doi:10.1038/s41467-018-04951-w

Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes

2018· review· en· W2883622734 on OpenAlexaff
Angli Xue, Yang Wu, Zhihong Zhu, Futao Zhang, Kathryn E. Kemper, Zhili Zheng, Loïc Yengo, Luke R. Lloyd‐Jones, Julia Sidorenko, Yeda Wu, Mawussé Agbessi, Habibul Ahsan, Isabel Alves, Anand Kumar Andiappan, Philip Awadalla, Alexis Battle, Frank Beutner, Marc Jan Bonder, Dorret I. Boomsma, Mark Christiansen, Annique Claringbould, Patrick Deelen, Tõnu Esko, Marie-Julie Favé, Lude Franke, Timothy M. Frayling, Sina A. Gharib, Gregory Gibson, Gibran Hemani, Rick Jansen, Mika Kähönen, Anette Kalnapenkis, Silva Kasela, Johannes Kettunen, Yungil Kim, Holger Kirsten, Péter Kovács, Knut Krohn, Jaanika Kronberg-Guzman, Viktorija Kukushkina, Zoltán Kutalik, Bernett Lee, Terho Lehtimäki, Markus Loeffler, Urko M. Marigorta, Andres Metspalu, Lili Milani, Martina Müller‐Nurasyid, Matthias Nauck, Michel G. Nivard, Brenda W.J.H. Penninx, Markus Perola, Natalia Pervjakova, Brandon L. Pierce, Joseph E. Powell, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Susan M. Ring, Samuli Ripatti, Olaf Rötzschke, Sina Rüeger, Ashis Saha, Markus Scholz, Katharina Schramm, Ilkka Seppälä, Michael Stümvoll, Patrick Sullivan, Alexander Teumer, Joachim Thiery, Tong Lin, Anke Tönjes, Jenny van Dongen, Joyce B. J. van Meurs, Joost Verlouw, Uwe Völker, Urmo Võsa, Hanieh Yaghootkar, Biao Zeng, Allan F. McRae, Peter M. Visscher, Jian Zeng, Jian Yang

Bibliographic record

VenueNature Communications · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsOntario Institute for Cancer Research
FundersNational Institute of Environmental Health SciencesNational Institute on AgingNational Institute of General Medical SciencesNational Institute of Mental HealthMedical Research CouncilNational Institutes of HealthUniversity of QueenslandNational Health and Medical Research CouncilWellcome Trust
KeywordsGenome-wide association studyBiologyEpigenomicsGeneticsDNA methylationGenetic associationExpression quantitative trait lociEpigeneticsGeneComputational biologyType 2 diabetesGenomeSingle-nucleotide polymorphismGene expressionGenotypeDiabetes mellitus

Abstract

fetched live from OpenAlex

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.

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)0.001
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 score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.003
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

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 head0.064
GPT teacher head0.410
Teacher spread0.345 · 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

Citations1,015
Published2018
Admission routes1
Has abstractyes

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