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Telomere length is not a main factor for the development of islet autoimmunity and type 1 diabetes in the TEDDY study.

Published version
Peer-reviewed

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Authors

Törn, Carina 
Liu, Xiang 
Onengut-Gumuscu, Suna 
Counts, Kevin M 
Moreno, Jose Leonardo 

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.

Description

Funder: Lund University

Keywords

Autoantibodies, Autoimmunity, Case-Control Studies, Child, Diabetes Mellitus, Type 1, Female, Genetic Predisposition to Disease, Genotype, Humans, Islets of Langerhans, Telomere

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

12

Publisher

Springer Science and Business Media LLC
Sponsorship
National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829, U01 DK63829)