title: The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.
abstract: OBJECTIVE
  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.
authors.affiliation: Pacific Northwest Diabetes Research Institute, Seattle, WA 98122, USA. wah@u.washington.edu
authors.forename: William A
authors.initials: WA
authors.lastname: Hagopian
authors.forename: Henry
authors.initials: H
authors.lastname: Erlich
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.forename: Anette G
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Olli
authors.initials: O
authors.lastname: Simell
authors.forename: Beena
authors.initials: B
authors.lastname: Akolkar
authors.forename: Robert
authors.initials: R
authors.lastname: Vogt
authors.forename: Alan
authors.initials: A
authors.lastname: Blair
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Krischer
authors.forename: JinXiong
authors.initials: J
authors.lastname: She
mesh_terms: D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004777:Environment; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000191:economics / Q000379:methods*; D011786:Quality Control; D012306:Risk
chemical_list: D006684:HLA-DR Antigens