The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History to the Progression from Multiple Autoantibodies to Type 1 Diabetes:A TEDDY Study Report: A TEDDY Study Report

Research output: Contribution to journalArticle

Abstract

This paper seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to T1D risk among autoantibody positive 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. The risk of progression to T1D was not different among those with or without a family history of T1D (p=0.39) nor HLA-DR-DQ genotypes (p=0.74). Age at developing multiple autoantibodies (HR=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 SNPs were associated with increased diabetes risk (rs10517086_A, [p=0.03], rs1534422_G, [p=0.006], and rs2327832_G in TNFAIP3 [p=0.03]), 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.

Details

Authors
  • Jeffrey P. Krischer
  • Xiang Liu
  • Åke Lernmark
  • William A. Hagopian
  • Marian J. Rewers
  • Jin-Xiong She
  • Jorma Toppari
  • Anette-G Ziegler
  • Beena Akolkar
  • TEDDY Study Group
Organisations
External organisations
  • University of South Florida
  • Skåne University Hospital
  • Pacific Northwest Diabetes Research Institute
  • University of Colorado
  • Augusta University
  • University of Turku
  • Technical University of Munich
  • National Institute of Diabetes and Digestive and Kidney Diseases
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • Journal Article
Original languageEnglish
Pages (from-to)3122-3129
JournalDiabetes
Volume66
Issue number12
Early online date2017 Sep 13
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes