| The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. | |
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MedLine Citation:
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PMID: 21564455 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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William A Hagopian; Henry Erlich; Ake Lernmark; Marian Rewers; Anette G Ziegler; Olli Simell; Beena Akolkar; Robert Vogt; Alan Blair; Jorma Ilonen; Jeffrey Krischer; JinXiong She; |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2011-05-12 |
Journal Detail:
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Title: Pediatric diabetes Volume: 12 ISSN: 1399-5448 ISO Abbreviation: Pediatr Diabetes Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-11-23 Completed Date: 2012-03-21 Revised Date: 2012-03-29 |
Medline Journal Info:
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Nlm Unique ID: 100939345 Medline TA: Pediatr Diabetes Country: Denmark |
Other Details:
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Languages: eng Pagination: 733-43 Citation Subset: IM |
Copyright Information:
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© 2011 John Wiley & Sons A/S. |
Affiliation:
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Pacific Northwest Diabetes Research Institute, Seattle, WA 98122, USA. wah@u.washington.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00279318 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cohort Studies Diabetes Mellitus, Type 1 / genetics* Environment* Genetic Predisposition to Disease* / genetics Genotype HLA-DR Antigens / genetics* Haplotypes Humans Infant Infant, Newborn Neonatal Screening / economics, methods* Quality Control Risk |
| Grant Support | |
ID/Acronym/Agency:
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DK 63790/DK/NIDDK NIH HHS; DK 63821/DK/NIDDK NIH HHS; DK 63829/DK/NIDDK NIH HHS; DK 63836/DK/NIDDK NIH HHS; DK 63861/DK/NIDDK NIH HHS; DK 63863/DK/NIDDK NIH HHS; DK 63865/DK/NIDDK NIH HHS; HHSN267200700014C//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/HLA-DR Antigens |
| Investigator | |
Investigator/Affiliation:
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Marian Rewers / ; Katherine Barriga / ; Judith Baxter / ; George Eisenbarth / ; Nicole Frank / ; Patricia Gesualdo / ; Michelle Hoffman / ; Lisa Ide / ; Jill Norris / ; Jessie Robinson / ; Kathleen Waugh / ; Jin-Xiong She / ; Desmond Schatz / ; Diane Hopkins / ; Leigh Steed / ; Angela Choate / ; Katherine Silvis / ; Meena Shankar / ; Jessica Leggett / ; Kim English / ; Richard McIndoe / ; Angela Dequesada / ; Michael Haller / ; Stephen W Anderson / ; Anette G Ziegler / ; Heike Boerschmann / ; Ezio Bonifacio / ; Melanie Bunk / ; Johannes Försch / ; Lydia Henneberger / ; Michael Hummel / ; Sandra Hummel / ; Gesa Joslowski / ; Mathilde Kersting / ; Annette Knopff / ; Nadja Kocher / ; Sibylle Koletzko / ; Stephanie Krause / ; Claudia Lauber / ; Ulrike Mollenhauer / ; Claudia Peplow / ; Maren Pflüger / ; Daniela Pöhlmann / ; Claudia Ramminger / ; Sargol Rash-Sur / ; Roswith Roth / ; Julia Schenkel / ; Leonore Thümer / ; Katja Voit / ; Christiane Winkler / ; Marina Zwilling / ; Olli G Simell / ; Kirsti Nanto-Salonen / ; Jorma Ilonen / ; Mikael Knip / ; Riitta Veijola / ; Tuula Simell / ; Heikki Hyöty / ; Suvi M Virtanen / ; Carina Kronberg-Kippilä / ; Maija Torma / ; Barbara Simell / ; Eeva Ruohonen / ; Minna Romo / ; Elina Mantymaki / ; Heidi Schroderus / ; Mia Nyblom / ; Aino Stenius / ; Ake Lernmark / ; Daniel Agardh / ; Peter Almgren / ; Eva Andersson / ; Carin Andrén-Aronsson / ; Maria Ask / ; Ulla-Marie Karlson / ; Corrado Cilio / ; Jenny Bremer / ; Emilie Ericson-Hallström / ; Thomas Gard / ; Joanna Gerardsson / ; Ulrika Gustavsson / ; Gertie Hansson / ; Monica Hansen / ; Susanne Hyberg / ; Rasmus Håkansson / ; Sten Ivarsson / ; Fredrik Johansen / ; Helena Larsson / ; Barbro Lernmark / ; Maria Markan / ; Theodosia Massadakis / ; Jessica Melin / ; Maria Månsson-Martinez / ; Anita Nilsson / ; Emma Nilson / ; Kobra Rahmati / ; Sara Rang / ; Monica Sedig Järvirova / ; Sara Sibthorpe / ; Birgitta Sjöberg / ; Carina Törn / ; Anne Wallin / ; Asa Wimar / ; William A Hagopian / ; Xiang Yan / ; Michael Killian / ; Claire Cowen Crouch / ; Kristen M Hay / ; Stephen Ayres / ; Carissa Adams / ; Brandi Bratrude / ; Greer Fowler / ; Czarina Franco / ; Carla Hammar / ; Diana Heaney / ; Patrick Marcus / ; Arlene Meyer / ; Denise Mulenga / ; Elizabeth Scott / ; Jennifer Skidmore / ; Erin Small / ; Joshua Stabbert / ; Viktoria Stepitova / ; Dorothy Becker / ; Margaret Franciscus / ; MaryEllen Dalmagro-Elias / ; Ashi Daftary / ; Jeffrey P Krischer / ; Michael Abbondondolo / ; Lori Ballard / ; Rasheedah Brown / ; David Cuthbertson / ; Christopher Eberhard / ; Veena Gowda / ; Hye-Seung Lee / ; Shu Liu / ; Kristian Lynch / ; Jamie Malloy / ; Cristina McCarthy / ; Wendy McLeod / ; Laura Smith / ; Stephen Smith / ; Susan Smith / ; Ulla Uusitalo / ; Kendra Vehik / ; Jimin Yang / ; Beena Akolkar / ; Thomas Briese / ; Henry Erlich / ; Suzanne Bennett Johnson / ; Steve Oberste / |
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