Evidence map›Paper›PMID 24988556›Full record

ArticleThe New England journal of medicine2014

Risk of pediatric celiac disease according to HLA haplotype and country.

Edwin Liu, Hye-Seung Lee, Carin A Aronsson, William A Hagopian, Sibylle Koletzko, Marian J Rewers, George S Eisenbarth, Polly J Bingley, Ezio Bonifacio, Ville Simell and 2 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 153 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

153 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Effects ofNutrients · 2019
    Trial
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. HLA-DQB1*03:01 strongly affects age of onset of type 1 narcolepsy independently of DQA1 and ethnicity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Article
  14. Article
  15. Non-Diarrheal Celiac Disease in Iraq: A Multicenter study.Middle East journal of digestive diseases · 2025
    Article
  16. One-Year Outcomes Among Children Identified With Celiac Disease Through a Mass Screening Program.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025
    Article
  17. Review
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Edwin LiuFrom the Digestive Health Institute, Children's Hospital Colorado (E.L.), and the Barbara Davis Center (E.L., M.J.R., G.S.E.), University of Colorado Denver, Aurora; the Pediatrics Epidemiology Center, University of South Florida, Tampa (H.-S.L.); the Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmo, Sweden (C.A.A., D.A.); Pacific Northwest Diabetes Research Institute, Seattle (W.A.H.); Dr. von Hauner Children's Hospital, Ludwig Maximilian University, Munich (S.K.), the Center for Regenerative Therapies Dresden, Technische Universitaet Dresden, Dresden (E.B.), and Forschergruppe Diabetes, Helmholz Zentrum München, Neuherberg (E.B.) - all in Germany; the School of Clinical Sciences, University of Bristol, Bristol, United Kingdom (P.J.B.); and the Department of Pediatrics, University of Turku, Turku University Hospital, Turku, Finland (V.S.).
Hye-Seung Lee
Carin A Aronsson
William A Hagopian
Sibylle Koletzko
Marian J Rewers
George S Eisenbarth
Polly J Bingley
Ezio Bonifacio
Ville Simell
Daniel Agardh
TEDDY Study Group

Funding

Data Coordinating Center (DCC)for the Consortium for Identification of EnvironmenUC4DK095300 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2011 to 2011
$56.0M
Data Coordinating CenterU01DK063790 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2002 to 2006
$50.1M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
Establish a Data Coordinating Center (DCC) for the Consortium for Identification UC4DK100238 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2014 to 2014
$28.9M
The Environmental Determinants of Diabetes in Young (TEDDY0U01DK063863 · NIDDK · HOSPITAL DISTRICT OF SOUTHWEST FINLAND · PI TOPPARI, JORMA · 2003 to 2022
$13.5M
The Environmental Triggers of Diabetes (TEDDY) in SwedenU01DK063861 · NIDDK · UNIVERSITY OF WASHINGTON · PI LERNMARK, AKE · 2003 to 2022
$13.4M
THE TEDDY STUDY - COLORADO CLINICAL CENTERU01DK063821 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI REWERS, MARIAN J · 2003 to 2022
$12.3M
The TEDDY Study: Georgia/Florida Clinical CenterU01DK063865 · NIDDK · MEDICAL COLLEGE OF GEORGIA (MCG) · PI MCINDOE, RICHARD A. · 2003 to 2022
$12.3M
UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
The Environmental Determinants of Diabetes in Youth: Washington Clinical CenterU01DK063829 · NIDDK · PACIFIC NORTHWEST RESEARCH INSTITUTE · PI HAGOPIAN, WILLIAM A. · 2003 to 2022
$11.8M
Type 1 Diabetes triggers: diet modification in neonatesU01DK063836 · NIDDK · FORSCHERGRUPPE DIABETES E. V. · PI ZIEGLER, ANETTE · 2003 to 2022
$6.2M
The Environmental Triggers of Diabetes (TEDDY)UC4DK063861 · NIDDK · LUNDS UNIVERSITET · PI LERNMARK, AKE · 2013 to 2013
$5.7M
NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR001082NIDDK NIH HHS U01 DK063790NIDDK NIH HHS U01 DK063821NIDDK NIH HHS U01 DK063829NIDDK NIH HHS U01 DK063836NIDDK NIH HHS U01 DK063861NIDDK NIH HHS U01 DK063863NIDDK NIH HHS U01 DK063865NIDDK NIH HHS U01 DK63790NIDDK NIH HHS U01 DK63821NIDDK NIH HHS U01 DK63829NIDDK NIH HHS U01 DK63836NIDDK NIH HHS U01 DK63861NIDDK NIH HHS U01 DK63863NIDDK NIH HHS U01 DK63865NIDDK NIH HHS UC4 DK063821NIDDK NIH HHS UC4 DK063829NIDDK NIH HHS UC4 DK063836NIDDK NIH HHS UC4 DK063861NIDDK NIH HHS UC4 DK063863NIDDK NIH HHS UC4 DK063865NIDDK NIH HHS UC4 DK095300NIDDK NIH HHS UC4 DK100238NIDDK NIH HHS UC4 DK63821NIDDK NIH HHS UC4 DK63829NIDDK NIH HHS UC4 DK63836NIDDK NIH HHS UC4 DK63861NIDDK NIH HHS UC4 DK63863NIDDK NIH HHS UC4 DK63865NIDDK NIH HHS UC4 DK95300
6 · The paper itself

Abstract

backgroundThe presence of HLA haplotype DR3-DQ2 or DR4-DQ8 is associated with an increased risk of celiac disease. In addition, nearly all children with celiac disease have serum antibodies against tissue transglutaminase (tTG).

methodsWe studied 6403 children with HLA haplotype DR3-DQ2 or DR4-DQ8 prospectively from birth in the United States, Finland, Germany, and Sweden. The primary end point was the development of celiac disease autoimmunity, which was defined as the presence of tTG antibodies on two consecutive tests at least 3 months apart. The secondary end point was the development of celiac disease, which was defined for the purpose of this study as either a diagnosis on biopsy or persistently high levels of tTG antibodies.

resultsThe median follow-up was 60 months (interquartile range, 46 to 77). Celiac disease autoimmunity developed in 786 children (12%). Of the 350 children who underwent biopsy, 291 had confirmed celiac disease; an additional 21 children who did not undergo biopsy had persistently high levels of tTG antibodies. The risks of celiac disease autoimmunity and celiac disease by the age of 5 years were 11% and 3%, respectively, among children with a single DR3-DQ2 haplotype, and 26% and 11%, respectively, among those with two copies (DR3-DQ2 homozygosity). In the adjusted model, the hazard ratios for celiac disease autoimmunity were 2.09 (95% confidence interval [CI], 1.70 to 2.56) among heterozygotes and 5.70 (95% CI, 4.66 to 6.97) among homozygotes, as compared with children who had the lowest-risk genotypes (DR4-DQ8 heterozygotes or homozygotes). Residence in Sweden was also independently associated with an increased risk of celiac disease autoimmunity (hazard ratio, 1.90; 95% CI, 1.61 to 2.25).

conclusionsChildren with the HLA haplotype DR3-DQ2, especially homozygotes, were found to be at high risk for celiac disease autoimmunity and celiac disease early in childhood. The higher risk in Sweden than in other countries highlights the importance of studying environmental factors associated with celiac disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Indexed as

Genetic Predisposition to DiseaseAntibodiesAutoimmune DiseasesCeliac DiseaseChild, PreschoolEuropeFemaleHLA-DQ AntigensHLA-DR3 AntigenHLA-DR4 AntigenHomozygoteHumansInfantInfant, NewbornKaplan-Meier EstimateMaleAntibodiesHLA-DQ2 antigenHLA-DQ8 antigenHLA-DQ AntigensHLA-DR3 AntigenHLA-DR4 AntigenTransglutaminases

Identifiers

PMID24988556
PMCPMC4163840

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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.