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

, ; Beyerlein, Andreas; Bonifacio, Ezio; Vehik, Kendra LU ; Hippich, Markus; Winkler, Christiane; Frohnert, Brigitte I.; Steck, Andrea K.; Hagopian, William A. and Krischer, Jeffrey P., et al. (2018) In Journal of Medical Genetics
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... (More)

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.

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in press
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keywords
diabetes, diagnostics tests, epidemiology, immunology (including allergy)
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Journal of Medical Genetics
publisher
BMJ Publishing Group
external identifiers
  • scopus:85054379240
ISSN
0022-2593
DOI
10.1136/jmedgenet-2018-105532
language
English
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yes
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053f056a-b0fd-46da-bfbc-c3b4b6ede46e
date added to LUP
2018-11-13 13:15:20
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2019-02-20 11:35:33
@article{053f056a-b0fd-46da-bfbc-c3b4b6ede46e,
  abstract     = {<p>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.</p>},
  author       = {,  and Beyerlein, Andreas and Bonifacio, Ezio and Vehik, Kendra and Hippich, Markus and Winkler, Christiane and Frohnert, Brigitte I. and Steck, Andrea K. and Hagopian, William A. and Krischer, Jeffrey P. and Lernmark, Åke and Rewers, Marian J. and She, Jin Xiong and Toppari, Jorma and Akolkar, Beena and Rich, Stephen S. and Ziegler, Anette G.},
  issn         = {0022-2593},
  keyword      = {diabetes,diagnostics tests,epidemiology,immunology (including allergy)},
  language     = {eng},
  month        = {10},
  publisher    = {BMJ Publishing Group},
  series       = {Journal of Medical Genetics},
  title        = {Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors : Results from the prospective TEDDY study},
  url          = {http://dx.doi.org/10.1136/jmedgenet-2018-105532},
  year         = {2018},
}