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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 602-605 |
| Number of pages | 4 |
| Journal | Journal of medical genetics |
| Volume | 56 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2019 |
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Keywords
- diabetes
- diagnostics tests
- epidemiology
- immunology (including allergy)
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
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; Hippich, Markus; Winkler, Christiane; Frohnert, Brigitte I.; Steck, Andrea K.; Hagopian, William A.; Krischer, Jeffrey P.; Lernmark, Åke; Rewers, Marian J.; She, Jin-Xiong; Toppari, Jorma; Akolkar, Beena; Rich, Stephen S.; Ziegler, Anette G.
In: Journal of medical genetics, Vol. 56, No. 9, 01.09.2019, p. 602-605.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors
T2 - Results from the prospective TEDDY study
AU - Beyerlein, Andreas
AU - Bonifacio, Ezio
AU - Vehik, Kendra
AU - Hippich, Markus
AU - Winkler, Christiane
AU - Frohnert, Brigitte I.
AU - Steck, Andrea K.
AU - Hagopian, William A.
AU - Krischer, Jeffrey P.
AU - Lernmark, Åke
AU - Rewers, Marian J.
AU - She, Jin-Xiong
AU - Toppari, Jorma
AU - Akolkar, Beena
AU - Rich, Stephen S.
AU - Ziegler, Anette G.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - diabetes
KW - diagnostics tests
KW - epidemiology
KW - immunology (including allergy)
UR - http://www.scopus.com/inward/record.url?scp=85054379240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054379240&partnerID=8YFLogxK
U2 - 10.1136/jmedgenet-2018-105532
DO - 10.1136/jmedgenet-2018-105532
M3 - Article
VL - 56
SP - 602
EP - 605
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
IS - 9
ER -