Evidence map›Paper›PMID 26782299›Full record

ArticleJournal of autoimmunity2016

Hypomethylation within gene promoter regions and type 1 diabetes in discordant monozygotic twins.

Emon Elboudwarej, Michael Cole, Farren B S Briggs, Alexandra Fouts, Pamela R Fain, Hong Quach, Diana Quach, Elizabeth Sinclair, Lindsey A Criswell, Julie A Lane and 3 more

Open access · greenAbstract readTwin Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of autoimmunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
9.6field-weighted citation impact, top 2% 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

29 citing papers in PubMed, 58 citations in OpenAlex.

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  16. Epigenetic Regulation in Etiology of Type 1 Diabetes Mellitus.International journal of molecular sciences · 2019
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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

13 authors at 5 institutions in 1 country.

Emon ElboudwarejDivision of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA.
Michael ColeDivision of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA.
Farren B S BriggsDivision of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA.
Alexandra FoutsUniversity of Colorado Denver, Barbara Davis Center for Childhood Diabetes, Denver, CO, USA.
Pamela R FainUniversity of Colorado Denver, Barbara Davis Center for Childhood Diabetes, Denver, CO, USA.
Hong QuachDivision of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA.
Diana QuachDivision of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA.
Elizabeth SinclairSan Francisco General Hospital and University of California, San Francisco (UCSF), San Francisco, CA, USA.
Lindsey A CriswellUniversity of California, San Francisco, Department of Medicine, USA.
Julie A LaneChildren's Hospital Oakland Research Institute, Oakland, CA, USA.
Andrea K SteckUniversity of Colorado Denver, Barbara Davis Center for Childhood Diabetes, Denver, CO, USA.
Lisa F BarcellosDivision of Epidemiology, Genetic Epidemiology and Genomics Laboratory, School of Public Health, University of California, Berkeley, CA, USA.
Janelle A NobleChildren's Hospital Oakland Research Institute, Oakland, CA, USA. Electronic address: jnoble@chori.org.
University of California, Berkeley · USUniversity of Colorado Denver · USChildren’s Institute · USSan Francisco General Hospital · USUniversity of California, San Francisco · US

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Multiple Autoantigens/Multiple Epitopes of Type 1DMR01DK032083 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI MICHELS, AARON W · 1986 to 2025
$6.9M
The genetic basis of type 1 diabetes autoimmunity in African AmericansR01DK061722 · NIDDK · CHILDREN'S HOSPITAL &RES CTR AT OAKLAND · PI NOBLE, JANELLE A · 2003 to 2013
$3.5M
The genetic basis of type 1 diabetes autoimmunity in African AmericansR56DK061722 · NIDDK · CHILDREN'S HOSPITAL & RES CTR AT OAKLAND · PI NOBLE, JANELLE A · 2008 to 2008
$311k
MULTIPLE AUTOANTIGENS OF PRETYPE I DMR37DK032083 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI EISENBARTH, GEORGE S · 1992 to 1999
–
NCRR NIH HHS UL1 RR024131NIAID NIH HHS AI50964NIDDK NIH HHS DK32083NIDDK NIH HHS DK61722NIDDK NIH HHS R01 DK032083NIDDK NIH HHS R01 DK061722NIDDK NIH HHS R37 DK032083NIDDK NIH HHS R56 DK061722
6 · The paper itself

Abstract

Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of whether epigenetic modification of the inherited DNA sequence may contribute to T1D susceptibility. Using the Infinium HumanMethylation450 BeadChip array (450k), a total of seven long-term disease-discordant monozygotic (MZ) twin pairs and five pairs of HLA-identical, disease-discordant non-twin siblings (NTS) were examined for associations between DNA methylation (DNAm) and T1D. Strong evidence for global hypomethylation of CpG sites within promoter regions in MZ twins with TID compared to twins without T1D was observed. DNA methylation data were then grouped into three categories of CpG sites for further analysis, including those within: 1) the major histocompatibility complex (MHC) region, 2) non-MHC genes with reported T1D association through genome wide association studies (GWAS), and 3) the epigenome, or remainder of sites that did not include MHC and T1D associated genes. Initial results showed modest methylation differences between discordant MZ twins for the MHC region and T1D-associated CpG sites, BACH2, INS-IGF2, and CLEC16A (DNAm difference range: 2.2%-5.0%). In the epigenome CpG set, the greatest methylation differences were observed in MAGI2, FANCC, and PCDHB16, (DNAm difference range: 6.9%-16.1%). These findings were not observed in the HLA-identical NTS pairs. Targeted pyrosequencing of five candidate CpG loci identified using the 450k array in the original discordant MZ twins produced similar results using control DNA samples, indicating strong agreement between the two DNA methylation profiling platforms. However, findings for the top five candidate CpG loci were not replicated in six additional T1D-discordant MZ twin pairs. Our results indicate global DNA hypomethylation within gene promoter regions may contribute to T1D; however, findings do not support the involvement of large DNAm differences at single CpG sites alone in T1D.

Indexed as

DNA MethylationPromoter Regions, GeneticTwins, MonozygoticAdolescentAdultChildChild, PreschoolCpG IslandsDiabetes Mellitus, Type 1Epigenesis, GeneticFemaleGenetic Predisposition to DiseaseHumansInfantMaleOrgan SpecificityDNA methylationMonozygotic twinsType 1 diabetes

Identifiers

PMID26782299
PMCPMC4792657
OpenAlexW2225123924

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.