The Environmental Determinants of Diabetes in the Young (TEDDY)

Genetic criteria and international diabetes risk screening of 421 000 infants

William A. Hagopian, Henry Erlich, Åke Lernmark, Marian Rewers, Anette G. Ziegler, Olli Simell, Beena Akolkar, Robert Vogt, Alan Blair, Jorma Ilonen, Jeffrey Krischer, Jin-Xiong She

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Aims: The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental factors influencing the development of type 1 diabetes (T1D) using intensive follow-up of children at elevated genetic risk. This study requires a cost-effective yet accurate screening strategy to identify the high-risk cohort. Methods: The TEDDY cohort was identified through newborn screening using human leukocyte antigen (HLA) class II genes based on criteria established with pre-TEDDY data. HLA typing was completed at six international centers using different genotyping methods that can achieve >98% accuracy. Results: TEDDY developed separate inclusion criteria for the general population (GP) and first-degree relatives (FDRs) of T1D patients. The FDR eligibility includes nine haplogenotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4b, DR4/1, DR4/13, DR4/9, and DR3/9) for broad HLA diversity, whereas the GP eligibility includes only the first four haplogenotypes with DRB1*0403 as an exclusion allele. TEDDY has screened 414 714 GP infants, of which 19 906 (4.8%) were eligible, whereas 1415 of the 6333 screened FDR infants (22.2%) were eligible. High-resolution confirmation testing of the eligible subjects indicated that the low-cost and low-resolution genotyping techniques employed at the screening centers yielded an accuracy of 99%. There were considerable variations in eligibility rates among the centers for GP (3.5-7.4%) and FDR (19-32%) subjects. The eligibility rates among US ethnic groups were 0.9, 1.3, 5.0, and 6.9% for Asians, Black, Caucasians, and Hispanics, respectively. Conclusions: Different low-cost and low-resolution genotyping methods are useful for the efficient and accurate identification of a high-risk cohort for follow-up based on the TEDDY HLA inclusion criteria (ClinicalTrials.gov NCT00279318).

Original languageEnglish (US)
Pages (from-to)733-743
Number of pages11
JournalPediatric Diabetes
Volume12
Issue number8
DOIs
StatePublished - Dec 1 2011

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HLA Antigens
Type 1 Diabetes Mellitus
Costs and Cost Analysis
Population
Genotyping Techniques
MHC Class II Genes
Hispanic Americans
Ethnic Groups
Alleles
Newborn Infant

Keywords

  • Autoimmunity
  • Genetic screening
  • Population based
  • Prediction
  • T1D

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

Cite this

The Environmental Determinants of Diabetes in the Young (TEDDY) : Genetic criteria and international diabetes risk screening of 421 000 infants. / Hagopian, William A.; Erlich, Henry; Lernmark, Åke; Rewers, Marian; Ziegler, Anette G.; Simell, Olli; Akolkar, Beena; Vogt, Robert; Blair, Alan; Ilonen, Jorma; Krischer, Jeffrey; She, Jin-Xiong.

In: Pediatric Diabetes, Vol. 12, No. 8, 01.12.2011, p. 733-743.

Research output: Contribution to journalArticle

Hagopian, WA, Erlich, H, Lernmark, Å, Rewers, M, Ziegler, AG, Simell, O, Akolkar, B, Vogt, R, Blair, A, Ilonen, J, Krischer, J & She, J-X 2011, 'The Environmental Determinants of Diabetes in the Young (TEDDY): Genetic criteria and international diabetes risk screening of 421 000 infants', Pediatric Diabetes, vol. 12, no. 8, pp. 733-743. https://doi.org/10.1111/j.1399-5448.2011.00774.x
Hagopian, William A. ; Erlich, Henry ; Lernmark, Åke ; Rewers, Marian ; Ziegler, Anette G. ; Simell, Olli ; Akolkar, Beena ; Vogt, Robert ; Blair, Alan ; Ilonen, Jorma ; Krischer, Jeffrey ; She, Jin-Xiong. / The Environmental Determinants of Diabetes in the Young (TEDDY) : Genetic criteria and international diabetes risk screening of 421 000 infants. In: Pediatric Diabetes. 2011 ; Vol. 12, No. 8. pp. 733-743.
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