Evidence map›Paper›PMID 32061050›Full record

ArticlePediatric diabetes2020

DNA methylation near the INS gene is associated with INS genetic variation (rs689) and type 1 diabetes in the Diabetes Autoimmunity Study in the Young.

Patrick M Carry, Lauren A Vanderlinden, Randi K Johnson, Fran Dong, Andrea K Steck, Brigitte I Frohnert, Marian Rewers, Ivana V Yang, Katerina Kechris, Jill M Norris

Open access · greenAbstract read
In one paragraph

Article in Pediatric diabetes, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Epigenetic Regulation of Pancreas Development and Function.Advances in anatomy, embryology, and cell biology · 2024
    Review
  4. Article
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Patrick M CarryDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-2989-7080
Lauren A VanderlindenDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Randi K JohnsonDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0001-9345-4439
Fran DongBarbara Davis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Andrea K SteckBarbara Davis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Brigitte I FrohnertBarbara Davis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-6636-4048
Marian RewersBarbara Davis Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Ivana V YangUniversity of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado.
Katerina KechrisDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Jill M NorrisDepartment of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
Colorado School of Public Health · USUniversity of Colorado Anschutz Medical Campus · US

Funding

Natural History of Pre-Diabetic Autoimmunity (DAISY)R01DK032493 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI REWERS, MARIAN J · 1986 to 2024
$9.3M
NUTRITIONAL ETIOLOGY OF PREDIABETIC AUTOIMMUNITYR01DK049654 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI NORRIS, JILL M · 1997 to 2011
$5.8M
Nutrigenetics & -genomics of Vitamin D and Omega-3 Fatty Acids in Type 1 DiabetesR01DK104351 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI NORRIS, JILL M · 2014 to 2018
$2.9M
Islet Autoimmunity Reversion as a Model of T1D ResiliencyR21AI142483 · NIAID · UNIVERSITY OF COLORADO DENVER · PI NORRIS, JILL M · 2019 to 2020
$428k
NIAID NIH HHS R21 AI142483NIDDK NIH HHS R01 DK032493NIDDK NIH HHS R01 DK049654NIDDK NIH HHS R01 DK104351
6 · The paper itself

Abstract

objectiveMechanisms underlying the role of non-human leukocyte antigen (HLA) genetic risk variants in type 1 diabetes (T1D) are poorly understood. We aimed to test the association between methylation and non-HLA genetic risk.

methodsWe conducted a methylation quantitative trait loci (mQTL) analysis in a nested case-control study from the Dietary Autoimmunity Study in the Young. Controls (n = 83) were frequency-matched to T1D cases (n = 83) based on age, race/ethnicity, and sample availability. We evaluated 13 non-HLA genetic markers known be associated with T1D. Genome-wide methylation profiling was performed on peripheral blood samples collected prior to T1D using the Illumina 450 K (discovery set) and infinium methylation EPIC beadchip (EPIC validation) platforms. Linear regression models, adjusting for age and sex, were used to test to each single nucleotide polymorphism (SNP) -probe combination. Logistic regression models were used to test the association between T1D and methylation levels among probes with a significant mQTL. A meta-analysis was used to combine odds ratios from the two platforms.

resultsWe identified 10 SNP-methylation probe pairs (false discovery rate (FDR) adjusted P < .05 and validation P < .05). Probes were associated with the GSDMB, C1QTNF6, IL27, and INS genes. The cg03366382 (OR: 1.9, meta-P = .0495), cg21574853 (OR: 2.5, meta-P = .0232), and cg25336198 (odds ratio: 6.6, meta-P = .0081) probes were significantly associated with T1D. The three probes were located upstream from the INS transcription start site.

conclusionsWe confirmed an association between DNA methylation and rs689 that has been identified in related studies. Measurements in our study preceded the onset of T1D suggesting methylation may have a role in the relationship between INS variation and T1D development.

Indexed as

AutoimmunityCase-Control StudiesChildChild, PreschoolCollagenDiabetes Mellitus, Type 1DNA MethylationFemaleGasderminsGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHLA-DR3 AntigenHLA-DR4 AntigenHumansInsulinC1qTNF6 protein, humanCollagenGasderminsGSDMB protein, humanHLA-DR3 AntigenHLA-DR4 AntigenInsulinInterleukinsMYDGF protein, humanNeoplasm ProteinsINSislet autoimmunitymethylationmQTLT1D

Identifiers

PMID32061050
PMCPMC7378362
OpenAlexW3005714302

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.