Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study

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@article{053f056ab0fd46dabfbcc3b4b6ede46e,
title = "Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study",
abstract = "Background: Progression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown. Methods: In 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression. Results: Islet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93). Conclusions: Genetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.",
keywords = "diabetes, diagnostics tests, epidemiology, immunology (including allergy)",
author = "Andreas Beyerlein and Ezio Bonifacio and Kendra Vehik and Markus Hippich and Christiane Winkler and Frohnert, {Brigitte I.} and Steck, {Andrea K.} and Hagopian, {William A.} and Krischer, {Jeffrey P.} and {\AA}ke Lernmark and Rewers, {Marian J.} and She, {Jin Xiong} and Jorma Toppari and Beena Akolkar and Rich, {Stephen S.} and Ziegler, {Anette G.} and {TEDDY Study Group}",
year = "2019",
doi = "10.1136/jmedgenet-2018-105532",
language = "English",
volume = "56",
pages = "602--605",
journal = "Journal of Medical Genetics",
issn = "0022-2593",
publisher = "BMJ Publishing Group",
number = "9",

}