Telomere length is not a main factor for the development of islet autoimmunity and type 1 diabetes in the TEDDY study
Authors: Törn Carina , Liu Xiang , Onengut-Gumuscu Suna , Counts Kevin M. , Moreno Jose Leonardo , Remedios Cassandra L. , Chen Wei-Min , LeFaive Jonathon , Butterworth Martha D. , Akolkar Beena , Krischer Jeffrey P. , Lernmark Åke , Rewers Marian , She Jin-Xiong , Toppari Jorma , Ziegler Anette-Gabriele , Ratan Aakrosh , Smith Albert V. , Hagopian William A. , Rich Stephen S. , Parikh Hemang M. ,   The TEDDY Study Group,   Colorado Clinical Center, Barbour Aaron , Bautista Kimberly , Baxter Judith , Felipe-Morales Daniel , Frohnert Brigitte I. , Stahl Marisa , Gesualdo Patricia , Haley Rachel , Hoffman Michelle , Karban Rachel , Liu Edwin , Munoz Alondra , Norris Jill , Peacock Stesha , Shorrosh Hanan , Steck Andrea , Stern Megan , Waugh Kathleen ,   Finland Clinical Center, Simell Olli G. , Adamsson Annika , Aaltonen Sanna-Mari , Ahonen Suvi , Åkerlund Mari , Hakola Leena , Hekkala Anne , Holappa Henna , Hyöty Heikki , Ikonen Anni , Ilonen Jorma , Jokipuu Sanna , Karlsson Leena , Kero Jukka , Kähönen Miia , Knip Mikael , Koivikko Minna-Liisa , Kokkonen Katja , Koskinen Merja , Koreasalo Mirva , Kurppa Kalle , Kuusela Salla , Kytölä Jarita , Lahtinen Sinikka , Laiho Jutta , Latva-aho Tiina , Leppänen Laura , Lindfors Katri , Lönnrot Maria , Mäntymäki Elina , Mattila Markus , Miettinen Maija , Multasuo Katja , Mykkänen Teija , Niininen Tiina , Niinistö Sari , Nyblom Mia , Oikarinen Sami , Ollikainen Paula , Othmani Zhian , Pohjola Sirpa , Rautanen Jenna , Riikonen Anne , Romo Minna , Simell Satu , Stenius Aino , Tossavainen Päivi , Vähä-Mäkilä Mari , Varjonen Eeva , Veijola Riitta , Viinikangas Irene , Virtanen Suvi M. ,   Georgia/Florida Clinical Center, Schatz Desmond , Hopkins Diane , Steed Leigh , Bryant Jennifer , Silvis Katherine , Haller Michael , Gardiner Melissa , McIndoe Richard , Sharma Ashok , Anderson Stephen W. , Jacobsen Laura , Marks John , Towe Paula D. ,   Germany Clinical Center, Bonifacio Ezio , Gezginci Cigdem , Heublein Anja , Hohoff Eva , Hummel Sandra , Knopff Annette , Koch Charlotte , Koletzko Sibylle , Ramminger Claudia , Roth Roswith , Schmidt Jennifer , Scholz Marlon , Stock Joanna , Warncke Katharina , Wendel Lorena , Winkler Christiane ,   Sweden Clinical Center, Agardh Daniel , Aronsson Carin Andrén , Ask Maria , Bennet Rasmus , Cilio Corrado , Dahlberg Susanne , Tsubarah Malin Goldman , Ericson-Hallström Emelie , Fors Annika Björne , Fransson Lina , Gard Thomas , Hansen Monika , Hyberg Susanne , Jonsdottir Berglind , Larsson Helena Elding , Lindström Marielle , Lundgren Markus , Maziarz Marlena , Martinez Maria Månsson , Melin Jessica , Mestan Zeliha , Nilsson Caroline , Nordh Yohanna , Rahmati Kobra , Ramelius Anita , Salami Falastin , Sjöberg Anette , Ulvenhag Ulrika , Wiktorsson Terese , Wimar Åsa ,   Washington Clinical Center, Killian Michael , Crouch Claire Cowen , Skidmore Jennifer , Chamberlain Christian , Fairman Brelon , Meyer Arlene , Meyer Jocelyn , Mulenga Denise , Powell Nole , Radtke Jared , Roy Shreya , Schmitt Davey , Zink Sarah ,   Pennsylvania Satellite Center, Becker Dorothy , Franciscus Margaret , Smith MaryEllen Dalmagro-Elias , Daftary Ashi , Klein Mary Beth , Yates Chrystal ,   Data Coordinating Center, Adusumali Rajesh , Austin-Gonzalez Sarah , Avendano Maryouri , Baethke Sandra , Burkhardt Brant , Cadigan Nicholas , Clasen Joanna , Gandolfo Laura , Garmeson Jennifer , Gowda Veena , Hsiao Belinda , Karges Christina , Liu Shu , Lynch Kristian F. , Malloy Jamie , McCarthy Cristina , Shaffer Michael , Smith Susan , Sulman Noah , Tamura Roy , Tewey Dena , Toth Michael , Uusitalo Ulla M. , Vehik Kendra , Vijayakandipan Ponni , Wroble Melissa , Yang Jimin , Young Kenneth ,   Past staff, Abbondondolo Michael , Ballard Lori , Brown Rasheedah , Cuthbertson David , Dankyi Stephen , Eberhard Christopher , Fiske Steven , Hadley David , Heyman Kathleen , Laras Francisco Perez , Lee Hye-Seung , Li Qian , Maguire Colleen , McLeod Wendy , Merrell Aubrie , Meulemans Steven , Quigley Ryan , Smith Laura ,   Autoantibody Reference Laboratories, Yu Liping , Miao Dongmei , Gillespie Kathleen , Williams Alistair , Chandler Kyla , Kelland Ilana , Khoud Yassin Ben , Randell Matthew ,   Genetics Laboratory, Farber Emily , Pickin Rebecca Roche , Davis Jonathan , Davis Jordan , Gallo Dan , Bonnie Jessica , Campolieto Paul ,   HLA Reference Laboratory, Chamberlain Christian , Radtke Jared , Zink Sarah , Erlich Previously Henry , Mack Steven J. , Fear Anna Lisa ,   Repository, Ke Sandra , Mulholland Niveen ,   Other contributors, Briese Thomas , Brusko Todd , Johnson Suzanne Bennett , McKinney Eoin F. , Pastinen Tomi , Triplett Eric W. 
Published: March 2022

The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8676 children, 3–4 months of age, born with HLA-susceptibility genotypes for islet autoimmunity (IA) and type 1 diabetes (T1D). Whole-genome sequencing (WGS) was performed in 1119 children in a nested case–control study design. Telomere length was estimated from WGS data using five tools: Computel, Telseq, Telomerecat, qMotif and Motif_counter. The estimated median telomere length was 5.10 kb (IQR 4.52–5.68 kb) using Computel. The age when the blood sample was drawn had a significant negative correlation with telomere length (P = 0.003). European children, particularly those from Finland (P = 0.041) and from Sweden (P = 0.001), had shorter telomeres than children from the U.S.A. Paternal age (P = 0.019) was positively associated with telomere length. First-degree relative status, presence of gestational diabetes in the mother, and maternal age did not have a significant impact on estimated telomere length. HLA-DR4/4 or HLA-DR4/X children had significantly longer telomeres compared to children with HLA-DR3/3 or HLA-DR3/9 haplogenotypes (P = 0.008). Estimated telomere length was not significantly different with respect to any IA (P = 0.377), IAA-first (P = 0.248), GADA-first (P = 0.248) or T1D (P = 0.861). These results suggest that telomere length has no major impact on the risk for IA, the first step to develop T1D. Nevertheless, telomere length was shorter in the T1D high prevalence populations, Finland and Sweden.