Dataset Information

The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.

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.

SUBMITTER: Hagopian WA

PROVIDER: S-EPMC3315186 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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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 WA Erlich Henry H Lernmark Ake A Rewers Marian M Ziegler Anette G AG Simell Olli O Akolkar Beena B Vogt Robert R Blair Alan A Ilonen Jorma J Krischer Jeffrey J She JinXiong J

Pediatric diabetes 20110512 8

<h4>Aims</h4>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.<h4>Methods</h4>The TEDDY cohort was identified through newborn screening using human leukocyte antigen (HLA) class II genes based on criteria established wit ...[more]

PMID: 21564455

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Project description:<p>The Environmental Determinants of Diabetes in the Young (TEDDY) Study investigates genetic and genetic-environmental interactions, including gestational events, childhood infections, dietary exposures, and other environmental factors after birth, in relation to the development of islet autoimmunity and type 1 diabetes (T1D). A consortium of six clinical centers assembled to participate in the development and implementation of the study to identify environmental triggers for the development of islet autoimmunity and T1D in genetically susceptible individuals. Beginning in 2004, the TEDDY study screened over 400,000 newborns for high-risk HLA-DR, DQ genotypes from both the general population and families already affected by T1D. The TEDDY study enrolled around 8,676 participants across six clinical centers worldwide (Finland, Germany, Sweden and three in the United States) in the 15-year prospective follow-up.</p> <p>Participants are followed every three months for islet autoantibody (IA) measurements with blood sampling until four years of age and then at least every six months until the age of 15. After the age of four, autoantibody positive participants continue to be followed at three month intervals and autoantibody negative participants are followed at six-month intervals. In addition to the analysis of autoantibodies, additional data and sample collection are performed at each visit. Parents collect monthly stool samples in early childhood. The parents also fill out questionnaires at regular intervals in connection with study visits and record information about diet and health status in the child's TEDDY Book between visits. Continued long-term follow-up of the currently active TEDDY participants will provide important scientific information on early childhood diet, reported and measured infections, vaccinations, and psychosocial stressors that may contribute to the development of type 1 diabetes and islet autoimmunity.</p> <p>Additional information on the TEDDY study is available in the following articles: The Environmental Determinants of Diabetes in the Young (TEDDY) Study. TEDDY Study Group. Annals of the New York Academy of Science, 2008 and TEDDY - The Environmental Determinants of Diabetes in the Young - An Observational Clinical Trial. Annals of the New York Academy of Science, 2006 <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=19120261">Annals of the New York Academy of Science, 2008</a> and TEDDY - The Environmental Determinants of Diabetes in the Young - An Observational Clinical Trial. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=17130573">Annals of the New York Academy of Science, 2006</a></p> <p> Details of the TEDDY protocol can be found in The Environmental Determinants of Diabetes in the Young (TEDDY): Genetic Criteria and International Diabetes Risk Screening of 421,000 infants. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=21564455">Pediatric Diabetes, 2011</a></p> <p> There are three substudies associated with the current TEDDY project release in dbGaP: <ul> <li>TEDDY SNP Array - <a href="study.cgi?study_id=phs001037">phs001037</a> with targeted SNP array data.</li> <li>TEDDY Microbiome - <a href="study.cgi?study_id=phs001443">phs001443</a> with metagenomic and 16S rRNA sequencing data.</li> <li>TEDDY Gene Expression - <a href="study.cgi?study_id=phs001562">phs001562</a> with gene expression data.</li> </ul> </p>

Dataset Information

The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.

Publications

The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.

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