In:
Journal of Medical Genetics, BMJ, Vol. 56, No. 9 ( 2019-09), p. 602-605
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-2593
,
1468-6244
DOI:
10.1136/jmedgenet-2018-105532
DOI:
10.1136/jmedgenet-2018-105532.supp1
DOI:
10.1136/jmedgenet-2018-105532.supp2
Language:
English
Publisher:
BMJ
Publication Date:
2019
detail.hit.zdb_id:
220881-7
detail.hit.zdb_id:
2009590-9
SSG:
12
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