Telomere length is not a main factor for the development of islet autoimmunity and type 1 diabetes in the TEDDY study
Carina Törn, Xiang Liu, Suna Önengüt-Gümüşcü, Kevin Counts, Jose Leonardo Moreno, Cassandra Remedios, Wei‐Min Chen, Jonathon LeFaive, Martha Butterworth, Beena Akolkar, Jeffrey P. Krischer, Åke Lernmark, Marian Rewers, Jin‐Xiong She, Jorma Toppari, Anette‐Gabriele Ziegler, Aakrosh Ratan, Albert V. Smith, William Hagopian, Stephen S. Rich, Hemang Parikh, The TEDDY Study Group, Aaron Barbour, Kimberly Bautista, Judith Baxter, Daniel Felipe-Morales, Brigitte I. Frohnert, Marisa Stahl, Patricia Gesualdo, Rachel Haley, Michelle Hoffman, Rachel Karban, Edwin Liu, Alondra Munoz, Jill M. Norris, Stesha Peacock, Hanan Shorrosh, Andrea K. Steck, Megan Stern, Kathleen Waugh, Olli Simell, Annika Adamsson, Sanna-Mari Aaltonen, Suvi Ahonen, Iris Erlund, Leena Hakola, Anne Hekkala, Henna Holappa, Heikki Hyöty, Anni Ikonen, Jorma Ilonen, Sanna Jokipuu, Leena Eklund Karlsson, Jukka Kero, Miia Kähönen, Mikael Knip, Minna-Liisa Koivikko, Katja Kokkonen, Merja Koskinen, Mirva Koreasalo, Kalle Kurppa, Salla Kuusela, Jarita Kytölä, Sinikka Lahtinen, Jutta E. Laiho, Tiina Latva-aho, Laura Leppänen, Katri Lindfors, Maria Lönnrot, Elina Mäntymäki, Markus Mattila, Maija E. Miettinen, Katja Multasuo, Teija Mykkänen, Tiina Niininen, Sari Niinistö, Mia Nyblom, Sami Oikarinen, Paula Ollikainen, Zhian Othmani, Sirpa Pohjola, Jenna Rautanen, Anne Riikonen, Minna Romo, Satu Simell, Aino Stenius, Päivi Tossavainen, Mari Vähä-Mäkilä, Eeva Varjonen, Riitta Veijola, Irene Viinikangas, Suvi Μ. Virtanen, Desmond Schatz, Diane Hopkins, Leigh Steed, Jennifer Bryant, Katherine Silvis, Michael Haller, Melissa Gardiner, Richard McIndoe
Abstract
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.