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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 LU orcid ; Rewers, Marian ; Ziegler, Anette G ; Simell, Olli ; Akolkar, Beena ; Vogt, Robert ; Blair, Alan and Ilonen, Jorma , et al. (2011) In Pediatric Diabetes 12. p.733-743
Abstract
Hagopian WA, Erlich H, Lernmark Å, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt Jr R, Blair A, Ilonen J, Krischer J, She J, and the TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. 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... (More)
Hagopian WA, Erlich H, Lernmark Å, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt Jr R, Blair A, Ilonen J, Krischer J, She J, and the TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. 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). (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pediatric Diabetes
volume
12
pages
733 - 743
publisher
Wiley-Blackwell
external identifiers
  • wos:000298170000010
  • pmid:21564455
  • scopus:80053036722
ISSN
1399-543X
DOI
10.1111/j.1399-5448.2011.00774.x
language
English
LU publication?
yes
id
1d38f243-137d-453c-9789-cb64d255cb53 (old id 1972851)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21564455?dopt=Abstract
date added to LUP
2016-04-04 07:00:39
date last changed
2022-02-05 21:56:37
@article{1d38f243-137d-453c-9789-cb64d255cb53,
  abstract     = {{Hagopian WA, Erlich H, Lernmark Å, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt Jr R, Blair A, Ilonen J, Krischer J, She J, and the TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. 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).}},
  author       = {{Hagopian, William A and Erlich, Henry and Lernmark, Åke and Rewers, Marian and Ziegler, Anette G and Simell, Olli and Akolkar, Beena and Vogt, Robert and Blair, Alan and Ilonen, Jorma and Krischer, Jeffrey and She, Jinxiong}},
  issn         = {{1399-543X}},
  language     = {{eng}},
  pages        = {{733--743}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Pediatric Diabetes}},
  title        = {{The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.}},
  url          = {{http://dx.doi.org/10.1111/j.1399-5448.2011.00774.x}},
  doi          = {{10.1111/j.1399-5448.2011.00774.x}},
  volume       = {{12}},
  year         = {{2011}},
}