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

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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; 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.; TEDDY Study Group.

In: Journal of Medical Genetics, Vol. 56, No. 9, 2019, p. 602-605.

Research output: Contribution to journalArticle

Harvard

Beyerlein, A, Bonifacio, E, Vehik, K, Hippich, M, Winkler, C, Frohnert, BI, Steck, AK, Hagopian, WA, Krischer, JP, Lernmark, Å, Rewers, MJ, She, JX, Toppari, J, Akolkar, B, Rich, SS, Ziegler, AG & TEDDY Study Group 2019, 'Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study', Journal of Medical Genetics, vol. 56, no. 9, pp. 602-605. https://doi.org/10.1136/jmedgenet-2018-105532

APA

Beyerlein, A., Bonifacio, E., Vehik, K., Hippich, M., Winkler, C., Frohnert, B. I., Steck, A. K., Hagopian, W. A., Krischer, J. P., Lernmark, Å., Rewers, M. J., She, J. X., Toppari, J., Akolkar, B., Rich, S. S., Ziegler, A. G., & TEDDY Study Group (2019). Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study. Journal of Medical Genetics, 56(9), 602-605. https://doi.org/10.1136/jmedgenet-2018-105532

CBE

Beyerlein A, Bonifacio E, Vehik K, Hippich M, Winkler C, Frohnert BI, Steck AK, Hagopian WA, Krischer JP, Lernmark Å, Rewers MJ, She JX, Toppari J, Akolkar B, Rich SS, Ziegler AG, TEDDY Study Group. 2019. Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: Results from the prospective TEDDY study. Journal of Medical Genetics. 56(9):602-605. https://doi.org/10.1136/jmedgenet-2018-105532

MLA

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Author

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. ; TEDDY Study Group. / Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors : Results from the prospective TEDDY study. In: Journal of Medical Genetics. 2019 ; Vol. 56, No. 9. pp. 602-605.

RIS

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.

AU - TEDDY Study Group

PY - 2019

Y1 - 2019

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)

U2 - 10.1136/jmedgenet-2018-105532

DO - 10.1136/jmedgenet-2018-105532

M3 - Article

C2 - 30287597

AN - SCOPUS:85054379240

VL - 56

SP - 602

EP - 605

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 9

ER -