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Record W2949346775 · doi:10.1038/s41467-019-10487-4

An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis

2019· article· en· W2949346775 on OpenAlexaff
Jun Liu, Elena Carnero‐Montoro, Jenny van Dongen, Samantha Lent, Ivana Nedeljković, Symen Ligthart, Pei-Chien Tsai, Tiphaine Martin, Pooja R. Mandaviya, Rick Jansen, Marjolein J. Peters, Liesbeth Duijts, Vincent W. V. Jaddoe, Henning Tiemeier, Janine F. Felix, Gonneke Willemsen, Eco J. C. de Geus, Audrey Y. Chu, Daniel Levy, Shih‐Jen Hwang, Jan Bressler, Rahul Gondalia, Elias Salfati, Christian Herder, Bertha Hidalgo, Toshiko Tanaka, Ann Zenobia Moore, Rozenn N. Lemaître, Min A. Jhun, Jennifer A. Smith, Nona Sotoodehnia, Stefania Bandinelli, Luigi Ferrucci, Donna K. Arnett, Harald Grallert, Themistocles L. Assimes, Lifang Hou, Andrea Baccarelli, Eric A. Whitsel, Ko Willems van Dijk, Najaf Amin, André G. Uitterlinden, Eric J.G. Sijbrands, Oscar H. Franco, Abbas Dehghan, Tim D. Spector, Josée Dupuis, Marie‐France Hivert, Jerome I. Rotter, James B. Meigs, James S. Pankow, Joyce B. J. van Meurs, Aaron Isaacs, Dorret I. Boomsma, Jordana T. Bell, Ayşe Demirkan, Cornelia M. van Duijn

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsUniversité de Sherbrooke
FundersNational Heart, Lung, and Blood InstituteEuropean CommissionEconomic and Social Research CouncilNational Institute of Diabetes and Digestive and Kidney DiseasesZonMwBiotechnology and Biological Sciences Research CouncilNational Institute on AgingHorizon 2020 Framework ProgrammeNederlandse Organisatie voor Wetenschappelijk OnderzoekAgence Nationale de la RechercheNational Institutes of HealthU.S. Department of Health and Human Services
KeywordsDNA methylationGlucose homeostasisBiologyEpigenomicsMethylationEpigeneticsIRS2EpigenomeType 2 diabetesInsulinInsulin receptorBioinformaticsGeneticsDiabetes mellitusGeneEndocrinologyInsulin resistanceGene expression

Abstract

fetched live from OpenAlex

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.

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: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.013
GPT teacher head0.334
Teacher spread0.321 · 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

Citations90
Published2019
Admission routes1
Has abstractyes

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