Evidence map›Paper›PMID 28520980›Full record

ArticleThe Journal of clinical endocrinology and metabolism2017

Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet Relatives at Risk for Type 1 Diabetes?

Andrea K Steck, Ping Xu, Susan Geyer, Maria J Redondo, Peter Antinozzi, John M Wentworth, Jay Sosenko, Suna Onengut-Gumuscu, Wei-Min Chen, Stephen S Rich and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Type 1 Diabetes Genetics Consortium.The Journal of clinical endocrinology and metabolism · 2025
    Review
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  9. Evaluating T cell responses prior to the onset of type 1 diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2022
    Article
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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

12 authors at 7 institutions in 2 countries.

Andrea K SteckBarbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
Ping XuHealth Informatics Institute, University of South Florida, Tampa, Florida 33612.
Susan GeyerHealth Informatics Institute, University of South Florida, Tampa, Florida 33612.
Maria J RedondoPediatric Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030.
Peter AntinozziCenter for Diabetes Research, Wake Forest School of Medicine, Winston Salem, North Carolina 27157.
John M WentworthDivision of Population Health and Immunity, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Jay SosenkoDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Miami School of Medicine, Miami, Florida 33136.
Suna Onengut-GumuscuCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22903.
Wei-Min ChenCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22903.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22903.
Alberto PuglieseDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Miami School of Medicine, Miami, Florida 33136.
Type 1 Diabetes TrialNet Study Group
University of Virginia · USUniversity of Miami · USUniversity of South Florida · USTexas Children's Hospital · USUniversity of Colorado Anschutz Medical Campus · USWake Forest University · USWalter and Eliza Hall Institute of Medical Research · AU

Funding

Northwest Clinical Center for Type 1 Diabetes - TrialNetU01DK061034 · NIDDK · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI GREENBAUM, CARLA J · 2001 to 2018
$10.3M
Type I Diabetes Trialnet at StsnfordU01DK061042 · NIDDK · STANFORD UNIVERSITY · PI WILSON, DARRELL M · 2001 to 2018
$8.5M
UCSF Trialnet: A Phase II Trial of Imatimib in New Onset Type I DiabetesU01DK061010 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GITELMAN, STEPHEN E · 2001 to 2018
$8.1M
Type 1 Diabetes-A Proposal for Prevention & InterventionU01DK085476 · NIDDK · UNIVERSITY OF MINNESOTA · PI MORAN, ANTOINETTE M. · 2009 to 2018
$7.1M
Prediction and Prevention of Type I DiabetesU01DK061058 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECKER, DOROTHY J · 2001 to 2018
$6.5M
TrialNet: University of Florida Clinical Center and NetworkU01DK085461 · NIDDK · UNIVERSITY OF FLORIDA · PI HALLER, MICHAEL JAMES · 2009 to 2018
$5.9M
TrialNet: Diabetes Type 1 PreventionU01DK085509 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI GOTTLIEB, PETER A · 2009 to 2018
$5.8M
Type 1 Diabetes TrialNet Clinical Center: Effects of Alefacept in New Onset T1DU01DK085499 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BAIDAL, DAVID · 2009 to 2018
$4.9M
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNetU01DK085465 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RUSSELL, WILLIAM E · 2009 to 2018
$4.8M
Type 1 Diabetes TrialNet: Clinical Center at Yale University (U01)U01DK085466 · NIDDK · YALE UNIVERSITY · PI HEROLD, KEVAN C · 2009 to 2018
$3.3M
Type 1 Diabetes TrialNet at Indiana University Clinical CenterU01DK085505 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI DIMEGLIO, LINDA A · 2009 to 2013
$3.0M
Type 1 Diabetes TrialNet: Clinical Centers (U01)U01DK085453 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI RASKIN, PHILIP · 2009 to 2013
$3.0M
NIDDK NIH HHS U01 DK061010NIDDK NIH HHS U01 DK061034NIDDK NIH HHS U01 DK061042NIDDK NIH HHS U01 DK061058NIDDK NIH HHS U01 DK085453NIDDK NIH HHS U01 DK085461NIDDK NIH HHS U01 DK085463NIDDK NIH HHS U01 DK085465NIDDK NIH HHS U01 DK085466NIDDK NIH HHS U01 DK085476NIDDK NIH HHS U01 DK085499NIDDK NIH HHS U01 DK085504NIDDK NIH HHS U01 DK085505NIDDK NIH HHS U01 DK085509NIDDK NIH HHS U01 DK103153NIDDK NIH HHS U01 DK103180NIDDK NIH HHS U01 DK103266NIDDK NIH HHS U01 DK107014
6 · The paper itself

Abstract

Context: Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. Objective: The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. Design and Setting: The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Participants: Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives. Main Outcome Measure: Effect of SNPs on the development of multiple Abs and T1D. Results: Cox proportional analyses included all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at initial screening, initial Ab type, and number. Factors involved in progression from single to multiple Abs included age at screening, relationship to proband, HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, factors involved in disease progression included glucose AUC, age at screening, Ab number, relationship to proband, HLA genotypes, rs6476839 (GLIS3), and rs7221109 (CCR7). In stratified analyses by age, glucose AUC, age at screening, sibling, HLA genotypes, rs6476839 (GLIS3), and rs4900384 (C14orf64) were significantly associated with progression to diabetes in participants <12 years old, whereas glucose AUC, sibling, rs3184504 (SH2B3), and rs4900384 (C14orf64) were significant in those ≥12. Conclusions: In conclusion, we identified five non-HLA SNPs associated with increased risk of progression from Ab positivity to disease that may improve risk stratification for prevention trials.

Indexed as

FamilyAdaptor Proteins, Signal TransducingAdolescentAdultAge FactorsArea Under CurveAutoantibodiesBlood GlucoseCation Transport ProteinsChildCTLA-4 AntigenDiabetes Mellitus, Type 1Disease ProgressionDNA-Binding ProteinsFemaleGenetic Predisposition to DiseaseAdaptor Proteins, Signal TransducingAutoantibodiesBlood GlucoseCation Transport ProteinsCCR7 protein, humanCTLA-4 AntigenCTLA4 protein, humanDNA-Binding ProteinsGLIS3 protein, humanGlutamate DecarboxylaseHLA-DQA1 antigenHLA-DQ alpha-ChainsHLA-DQB1 antigenHLA-DQ beta-ChainsHLA-DRB1 ChainsInsulinIntracellular Signaling Peptides and Proteinsislet cell antibodyProteinsReceptor-Like Protein Tyrosine Phosphatases, Class 8Receptors, CCR7Repressor ProteinsRNA, Long NoncodingSH2B3 protein, humanSLC30A8 protein, humanTrans-ActivatorsTranscription FactorsZinc Transporter 8

Identifiers

PMID28520980
PMCPMC5546868
OpenAlexW2614544875

What OpenQuestion holds

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Registered trials

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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.