The influence of type 1 diabetes genetic susceptibility regions, age, sex, and family history on the progression from multiple autoantibodies to type 1 diabetes: A teddy study report

Jeffrey P. Krischer, Xiang Liu, Åke Lernmark, William A. Hagopian, Marian J. Rewers, Jin Xiong She, Jorma Toppari, Anette G. Ziegler, Beena Akolkar

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3122-3129
Number of pages8
JournalDiabetes
Volume66
Issue number12
DOIs
StatePublished - Dec 1 2017

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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