RT Journal Article
SR Electronic
T1 Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 602
OP 605
DO 10.1136/jmedgenet-2018-105532
VO 56
IS 9
A1 Andreas Beyerlein
A1 Ezio Bonifacio
A1 Kendra Vehik
A1 Markus Hippich
A1 Christiane Winkler
A1 Brigitte I Frohnert
A1 Andrea K Steck
A1 William A Hagopian
A1 Jeffrey P Krischer
A1 Åke Lernmark
A1 Marian J Rewers
A1 Jin-Xiong She
A1 Jorma Toppari
A1 Beena Akolkar
A1 Stephen S Rich
A1 Anette-G Ziegler
A1 ,
YR 2019
UL http://jmg.bmj.com/content/56/9/602.abstract
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.