PMID- 21564455 OWN - NLM STAT- MEDLINE DCOM- 20120321 LR - 20240422 IS - 1399-5448 (Electronic) IS - 1399-543X (Print) IS - 1399-543X (Linking) VI - 12 IP - 8 DP - 2011 Dec TI - The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. PG - 733-43 LID - 10.1111/j.1399-5448.2011.00774.x [doi] AB - 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. CI - (c) 2011 John Wiley & Sons A/S. FAU - Hagopian, William A AU - Hagopian WA AD - Pacific Northwest Diabetes Research Institute, Seattle, WA 98122, USA. wah@u.washington.edu FAU - Erlich, Henry AU - Erlich H FAU - Lernmark, Ake AU - Lernmark A FAU - Rewers, Marian AU - Rewers M FAU - Ziegler, Anette G AU - Ziegler AG FAU - Simell, Olli AU - Simell O FAU - Akolkar, Beena AU - Akolkar B FAU - Vogt, Robert Jr AU - Vogt R Jr FAU - Blair, Alan AU - Blair A FAU - Ilonen, Jorma AU - Ilonen J FAU - Krischer, Jeffrey AU - Krischer J FAU - She, JinXiong AU - She J CN - TEDDY Study Group LA - eng SI - ClinicalTrials.gov/NCT00279318 GR - DK 63865/DK/NIDDK NIH HHS/United States GR - HHSN267200700014C/DK/NIDDK NIH HHS/United States GR - U01 DK063865-10/DK/NIDDK NIH HHS/United States GR - U01 DK063861/DK/NIDDK NIH HHS/United States GR - DK 63790/DK/NIDDK NIH HHS/United States GR - DK 63861/DK/NIDDK NIH HHS/United States GR - U01 DK063863-10/DK/NIDDK NIH HHS/United States GR - U01 DK063861-10/DK/NIDDK NIH HHS/United States GR - U01 DK063790-05/DK/NIDDK NIH HHS/United States GR - U01 DK063821/DK/NIDDK NIH HHS/United States GR - DK 63821/DK/NIDDK NIH HHS/United States GR - U01 DK063829-09/DK/NIDDK NIH HHS/United States GR - DK 63863/DK/NIDDK NIH HHS/United States GR - U01 DK063829/DK/NIDDK NIH HHS/United States GR - U01 DK063865/DK/NIDDK NIH HHS/United States GR - UC4 DK095300/DK/NIDDK NIH HHS/United States GR - DK 63829/DK/NIDDK NIH HHS/United States GR - UC4 DK063861/DK/NIDDK NIH HHS/United States GR - UC4 DK063829/DK/NIDDK NIH HHS/United States GR - U01 DK063821-10/DK/NIDDK NIH HHS/United States GR - UC4 DK063821/DK/NIDDK NIH HHS/United States GR - UC4 DK063865/DK/NIDDK NIH HHS/United States GR - U01 DK063863/DK/NIDDK NIH HHS/United States GR - DK 63836/DK/NIDDK NIH HHS/United States GR - U01 DK063790/DK/NIDDK NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20110512 PL - Denmark TA - Pediatr Diabetes JT - Pediatric diabetes JID - 100939345 RN - 0 (HLA-DR Antigens) SB - IM MH - Cohort Studies MH - Diabetes Mellitus, Type 1/*genetics MH - *Environment MH - *Genetic Predisposition to Disease/genetics MH - Genotype MH - HLA-DR Antigens/*genetics MH - Haplotypes MH - Humans MH - Infant MH - Infant, Newborn MH - Neonatal Screening/economics/*methods MH - Quality Control MH - Risk PMC - PMC3315186 MID - NIHMS365277 FIR - Rewers, Marian IR - Rewers M FIR - Barriga, Katherine IR - Barriga K FIR - Baxter, Judith IR - Baxter J FIR - Eisenbarth, George IR - Eisenbarth G FIR - Frank, Nicole IR - Frank N FIR - Gesualdo, Patricia IR - Gesualdo P FIR - Hoffman, Michelle IR - Hoffman M FIR - Ide, Lisa IR - Ide L FIR - Norris, Jill IR - Norris J FIR - Robinson, Jessie IR - Robinson J FIR - Waugh, Kathleen IR - Waugh K FIR - She, Jin-Xiong IR - She JX FIR - Schatz, Desmond IR - Schatz D FIR - Hopkins, Diane IR - Hopkins D FIR - Steed, Leigh IR - Steed L FIR - Choate, Angela IR - Choate A FIR - Silvis, Katherine IR - Silvis K FIR - Shankar, Meena IR - Shankar M FIR - Leggett, Jessica IR - Leggett J FIR - English, Kim IR - English K FIR - McIndoe, Richard IR - McIndoe R FIR - Dequesada, Angela IR - Dequesada A FIR - Haller, Michael IR - Haller M FIR - Anderson, Stephen W IR - Anderson SW FIR - Ziegler, Anette G IR - Ziegler AG FIR - Boerschmann, Heike IR - Boerschmann H FIR - Bonifacio, Ezio IR - Bonifacio E FIR - Bunk, Melanie IR - Bunk M FIR - Forsch, Johannes IR - Forsch J FIR - Henneberger, Lydia IR - Henneberger L FIR - Hummel, Michael IR - Hummel M FIR - Hummel, Sandra IR - Hummel S FIR - Joslowski, Gesa IR - Joslowski G FIR - Kersting, Mathilde IR - Kersting M FIR - Knopff, Annette IR - Knopff A FIR - Kocher, Nadja IR - Kocher N FIR - Koletzko, Sibylle IR - Koletzko S FIR - Krause, Stephanie IR - Krause S FIR - Lauber, Claudia IR - Lauber C FIR - Mollenhauer, Ulrike IR - Mollenhauer U FIR - Peplow, Claudia IR - Peplow C FIR - Pfluger, Maren IR - Pfluger M FIR - Pohlmann, Daniela IR - Pohlmann D FIR - Ramminger, Claudia IR - Ramminger C FIR - Rash-Sur, Sargol IR - Rash-Sur S FIR - Roth, Roswith IR - Roth R FIR - Schenkel, Julia IR - Schenkel J FIR - Thumer, Leonore IR - Thumer L FIR - Voit, Katja IR - Voit K FIR - Winkler, Christiane IR - Winkler C FIR - Zwilling, Marina IR - Zwilling M FIR - Simell, Olli G IR - Simell OG FIR - Nanto-Salonen, Kirsti IR - Nanto-Salonen K FIR - Ilonen, Jorma IR - Ilonen J FIR - Knip, Mikael IR - Knip M FIR - Veijola, Riitta IR - Veijola R FIR - Simell, Tuula IR - Simell T FIR - Hyoty, Heikki IR - Hyoty H FIR - Virtanen, Suvi M IR - Virtanen SM FIR - Kronberg-Kippila, Carina IR - Kronberg-Kippila C FIR - Torma, Maija IR - Torma M FIR - Simell, Barbara IR - Simell B FIR - Ruohonen, Eeva IR - Ruohonen E FIR - Romo, Minna IR - Romo M FIR - Mantymaki, Elina IR - Mantymaki E FIR - Schroderus, Heidi IR - Schroderus H FIR - Nyblom, Mia IR - Nyblom M FIR - Stenius, Aino IR - Stenius A FIR - Lernmark, Ake IR - Lernmark A FIR - Agardh, Daniel IR - Agardh D FIR - Almgren, Peter IR - Almgren P FIR - Andersson, Eva IR - Andersson E FIR - Andren-Aronsson, Carin IR - Andren-Aronsson C FIR - Ask, Maria IR - Ask M FIR - Karlson, Ulla-Marie IR - Karlson UM FIR - Cilio, Corrado IR - Cilio C FIR - Bremer, Jenny IR - Bremer J FIR - Ericson-Hallstrom, Emilie IR - Ericson-Hallstrom E FIR - Gard, Thomas IR - Gard T FIR - Gerardsson, Joanna IR - Gerardsson J FIR - Gustavsson, Ulrika IR - Gustavsson U FIR - Hansson, Gertie IR - Hansson G FIR - Hansen, Monica IR - Hansen M FIR - Hyberg, Susanne IR - Hyberg S FIR - Hakansson, Rasmus IR - Hakansson R FIR - Ivarsson, Sten IR - Ivarsson S FIR - Johansen, Fredrik IR - Johansen F FIR - Larsson, Helena IR - Larsson H FIR - Lernmark, Barbro IR - Lernmark B FIR - Markan, Maria IR - Markan M FIR - Massadakis, Theodosia IR - Massadakis T FIR - Melin, Jessica IR - Melin J FIR - Mansson-Martinez, Maria IR - Mansson-Martinez M FIR - Nilsson, Anita IR - Nilsson A FIR - Nilson, Emma IR - Nilson E FIR - Rahmati, Kobra IR - Rahmati K FIR - Rang, Sara IR - Rang S FIR - Jarvirova, Monica Sedig IR - Jarvirova MS FIR - Sibthorpe, Sara IR - Sibthorpe S FIR - Sjoberg, Birgitta IR - Sjoberg B FIR - Torn, Carina IR - Torn C FIR - Wallin, Anne IR - Wallin A FIR - Wimar, Asa IR - Wimar A FIR - Hagopian, William A IR - Hagopian WA FIR - Yan, Xiang IR - Yan X FIR - Killian, Michael IR - Killian M FIR - Crouch, Claire Cowen IR - Crouch CC FIR - Hay, Kristen M IR - Hay KM FIR - Ayres, Stephen IR - Ayres S FIR - Adams, Carissa IR - Adams C FIR - Bratrude, Brandi IR - Bratrude B FIR - Fowler, Greer IR - Fowler G FIR - Franco, Czarina IR - Franco C FIR - Hammar, Carla IR - Hammar C FIR - Heaney, Diana IR - Heaney D FIR - Marcus, Patrick IR - Marcus P FIR - Meyer, Arlene IR - Meyer A FIR - Mulenga, Denise IR - Mulenga D FIR - Scott, Elizabeth IR - Scott E FIR - Skidmore, Jennifer IR - Skidmore J FIR - Small, Erin IR - Small E FIR - Stabbert, Joshua IR - Stabbert J FIR - Stepitova, Viktoria IR - Stepitova V FIR - Becker, Dorothy IR - Becker D FIR - Franciscus, Margaret IR - Franciscus M FIR - Dalmagro-Elias, MaryEllen IR - Dalmagro-Elias M FIR - Daftary, Ashi IR - Daftary A FIR - Krischer, Jeffrey P IR - Krischer JP FIR - Abbondondolo, Michael IR - Abbondondolo M FIR - Ballard, Lori IR - Ballard L FIR - Brown, Rasheedah IR - Brown R FIR - Cuthbertson, David IR - Cuthbertson D FIR - Eberhard, Christopher IR - Eberhard C FIR - Gowda, Veena IR - Gowda V FIR - Lee, Hye-Seung IR - Lee HS FIR - Liu, Shu IR - Liu S FIR - Lynch, Kristian IR - Lynch K FIR - Malloy, Jamie IR - Malloy J FIR - McCarthy, Cristina IR - McCarthy C FIR - McLeod, Wendy IR - McLeod W FIR - Smith, Laura IR - Smith L FIR - Smith, Stephen IR - Smith S FIR - Smith, Susan IR - Smith S FIR - Uusitalo, Ulla IR - Uusitalo U FIR - Vehik, Kendra IR - Vehik K FIR - Yang, Jimin IR - Yang J FIR - Akolkar, Beena IR - Akolkar B FIR - Briese, Thomas IR - Briese T FIR - Erlich, Henry IR - Erlich H FIR - Johnson, Suzanne Bennett IR - Johnson SB FIR - Oberste, Steve IR - Oberste S EDAT- 2011/05/14 06:00 MHDA- 2012/03/22 06:00 PMCR- 2012/12/01 CRDT- 2011/05/14 06:00 PHST- 2011/05/14 06:00 [entrez] PHST- 2011/05/14 06:00 [pubmed] PHST- 2012/03/22 06:00 [medline] PHST- 2012/12/01 00:00 [pmc-release] AID - 10.1111/j.1399-5448.2011.00774.x [doi] PST - ppublish SO - Pediatr Diabetes. 2011 Dec;12(8):733-43. doi: 10.1111/j.1399-5448.2011.00774.x. Epub 2011 May 12.