The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants
William A Hagopian, Henry Erlich, Ake Lernmark, Marian Rewers, Anette G Ziegler, Olli Simell, Beena Akolkar, Robert Vogt Jr, Alan Blair, Jorma Ilonen, Jeffrey Krischer, JinXiong She, TEDDY Study Group, 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, William A Hagopian, Henry Erlich, Ake Lernmark, Marian Rewers, Anette G Ziegler, Olli Simell, Beena Akolkar, Robert Vogt Jr, Alan Blair, Jorma Ilonen, Jeffrey Krischer, JinXiong She, TEDDY Study Group, 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
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.
Trial registration: ClinicalTrials.gov NCT00279318.
© 2011 John Wiley & Sons A/S.
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Source: PubMed