TY - JOUR
T1 - The influence of type 1 diabetes genetic susceptibility regions, age, sex, and family history on the progression from multiple autoantibodies to type 1 diabetes
T2 - A teddy study report
AU - Krischer, Jeffrey P.
AU - Liu, Xiang
AU - Lernmark, Åke
AU - Hagopian, William A.
AU - Rewers, Marian J.
AU - She, Jin Xiong
AU - Toppari, Jorma
AU - Ziegler, Anette G.
AU - Akolkar, Beena
N1 - Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two ormore diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibodypositive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, INS gene (rs1004446-A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium (T1DGC). The risk of progression to T1D was not different among those with or without a family history of T1D (P = 0.39) or HLA-DR-DQ genotypes (P = 0.74). Age at developing multiple autoantibodies (hazard ratio = 0.96 per 1-month increase in age; 95% CI 0.95, 0.97; P < 0.001) and the type of first autoantibody (when more than a single autoantibody was the first-appearing indication of seroconversion [P = 0.006]) were statistically significant. Female sex was also a significant risk factor (P = 0.03). Three single nucleotide polymorphisms were associated with increased diabetes risk (rs10517086-A [P = 0.03], rs1534422-G [P = 0.006], and rs2327832-G [P = 0.03] in TNFAIP3) and one with decreased risk (rs1004446-A in INS [P = 0.006]). The TEDDY data suggest that non-HLA gene polymorphisms may play a different role in the initiation of autoimmunity than they do in progression to T1D once autoimmunity has appeared. The strength of these associations may be related to the age of the population and the high-risk HLA-DR-DQ subtypes studied.
AB - This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two ormore diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibodypositive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, INS gene (rs1004446-A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium (T1DGC). The risk of progression to T1D was not different among those with or without a family history of T1D (P = 0.39) or HLA-DR-DQ genotypes (P = 0.74). Age at developing multiple autoantibodies (hazard ratio = 0.96 per 1-month increase in age; 95% CI 0.95, 0.97; P < 0.001) and the type of first autoantibody (when more than a single autoantibody was the first-appearing indication of seroconversion [P = 0.006]) were statistically significant. Female sex was also a significant risk factor (P = 0.03). Three single nucleotide polymorphisms were associated with increased diabetes risk (rs10517086-A [P = 0.03], rs1534422-G [P = 0.006], and rs2327832-G [P = 0.03] in TNFAIP3) and one with decreased risk (rs1004446-A in INS [P = 0.006]). The TEDDY data suggest that non-HLA gene polymorphisms may play a different role in the initiation of autoimmunity than they do in progression to T1D once autoimmunity has appeared. The strength of these associations may be related to the age of the population and the high-risk HLA-DR-DQ subtypes studied.
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U2 - 10.2337/db17-0261
DO - 10.2337/db17-0261
M3 - Article
C2 - 28903990
AN - SCOPUS:85035347149
SN - 0012-1797
VL - 66
SP - 3122
EP - 3129
JO - Diabetes
JF - Diabetes
IS - 12
ER -