Evidence map›Paper›PMID 18252895›Full record

ArticleDiabetes2008

HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families.

Henry Erlich, Ana Maria Valdes, Janelle Noble, Joyce A Carlson, Mike Varney, Pat Concannon, Josyf C Mychaleckyj, John A Todd, Persia Bonella, Anna Lisa Fear and 4 more

Registry-linked trialAbstract readMulticenter Study
In one paragraph

Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01477476 (Anti-IL-1 Treatment in Children Diabetic Keto-Acidosis), which is not on this map. Cited by 450 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
450citing papers in PubMed, 4 pooled it
27.1field-weighted citation impact, top 1% 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.

NCT01477476 phase2withdrawnnot on this mapstarted 2012, after this paper: background citation

Anti-IL-1 Treatment in Children Diabetic Keto-Acidosis (DKA) at Diagnosis of Type 1 Diabetes.

TypeinterventionalSponsorUniversity of Colorado, DenverRan2012 to 2016Enrolled0ConditionsType I DiabetesArmsAnakinra, Placebo Comparator
3 · Its place in the literature

Who cites it

450 citing papers in PubMed, 4 syntheses or guidelines pooled it, 771 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Article
  7. Review
  8. Article
  9. Article
  10. Type 1 Diabetes Mellitus Pathogenesis: Mechanisms, Early Diagnostic Strategies, and Emerging Therapeutic Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  11. Article
  12. Article
  13. Shared trans-ancestry architecture of HLA-mediated disease risk in themedRxiv : the preprint server for health sciences · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. [Role of HLA genetic variants in autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  18. Review
  19. Review
  20. Review

390 more citing papers are in PubMed but not listed here.

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

14 authors at 5 institutions in 4 countries.

Henry ErlichRoche Molecular Systems, 1145 Atlantic Ave., Alameda, CA 94501, USA. Henry.Erlich@Roche.com
Ana Maria Valdes
Janelle Noble
Joyce A Carlson
Mike Varney
Pat Concannon
Josyf C Mychaleckyj
John A Todd
Persia Bonella
Anna Lisa Fear
Eva Lavant
Anthony Louey
Priscilla Moonsamy
Type 1 Diabetes Genetics Consortium
Australian Red Cross Lifeblood · AUGeneTrace Systems (United States) · USMalmö University · SEUniversity of Virginia · USUniversity of Cambridge · GB

Funding

Type 1 Diabetes Genetics ConsortiumU01DK062418 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI RICH, STEPHEN S. · 2002 to 2007
$59.8M
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
NIDDK NIH HHS R01 DK061722NIDDK NIH HHS U01 DK062418NIDDK NIH HHS U01-DK-062418Wellcome Trust
6 · The paper itself

Abstract

objectiveThe Type 1 Diabetes Genetics Consortium has collected type 1 diabetic families worldwide for genetic analysis. The major genetic determinants of type 1 diabetes are alleles at the HLA-DRB1 and DQB1 loci, with both susceptible and protective DR-DQ haplotypes present in all human populations. The aim of this study is to estimate the risk conferred by specific DR-DQ haplotypes and genotypes. RESEARCH DESIGN AND

methodsSix hundred and seven Caucasian families and 38 Asian families were typed at high resolution for the DRB1, DQA1, and DQB1 loci. The association analysis was performed by comparing the frequency of DR-DQ haplotypes among the chromosomes transmitted to an affected child with the frequency of chromosomes not transmitted to any affected child.

resultsA number of susceptible, neutral, and protective DR-DQ haplotypes have been identified, and a statistically significant hierarchy of type 1 diabetes risk has been established. The most susceptible haplotypes are the DRB1*0301-DQA1*0501-DQB1*0201 (odds ratio [OR] 3.64) and the DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB*0302, and DRB1*0402-DQA1*0301-DQB1*0302 haplotypes (ORs 11.37, 8.39, and 3.63), followed by the DRB1*0404-DQA1*0301-DQB1*0302 (OR 1.59) and the DRB1*0801-DQB1*0401-DQB1*0402 (OR 1.25) haplotypes. The most protective haplotypes are DRB1*1501-DQA1*0102-DQB1*0602 (OR 0.03), DRB1*1401-DQA1*0101-DQB1*0503 (OR 0.02), and DRB1*0701-DQA1*0201-DQB1*0303 (OR 0.02).

conclusionsSpecific combinations of alleles at the DRB1, DQA1, and DQB1 loci determine the extent of haplotypic risk. The comparison of closely related DR-DQ haplotype pairs with different type 1 diabetes risks allowed identification of specific amino acid positions critical in determining disease susceptibility. These data also indicate that the risk associated with specific HLA haplotypes can be influenced by the genotype context and that the trans-complementing heterodimer encoded by DQA1*0501 and DQB1*0302 confers very high risk.

Indexed as

Age of OnsetAsian PeopleChildChild, PreschoolDiabetes Mellitus, Type 1FamilyFemaleGenetic Predisposition to DiseaseGenotypeHLA-DQ alpha-ChainsHLA-DQ AntigensHLA-DQ beta-ChainsHLA-DR AntigensHLA-DRB1 ChainsHumansMaleHLA-DQA1 antigenHLA-DQ alpha-ChainsHLA-DQ AntigensHLA-DQB1 antigenHLA-DQ beta-ChainsHLA-DR AntigensHLA-DRB1*03:01 antigenHLA-DRB1*04:01 antigenHLA-DRB1*04:02 antigenHLA-DRB1 Chains

Identifiers

PMID18252895
PMCPMC4103420
OpenAlexW2157754662

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.