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Åke Lernmark

Principal investigator

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Role of Type 1 diabetes associated SNPs on risk of autoantibody positivity in the TEDDY Study.

Author

  • Carina Törn
  • David Hadley
  • Hye-Seung Lee
  • William Hagopian
  • Åke Lernmark
  • Olli Simell
  • Marian Rewers
  • Anette Ziegler
  • Desmond Schatz
  • Beena Akolkar
  • Suna Onengut-Gumuscu
  • Wei-Min Chen
  • Jorma Toppari
  • Juha Mykkänen
  • Jorma Ilonen
  • Stephen S Rich
  • Jin-Xiong She
  • Andrea K Steck
  • Jeffrey Krischer

Summary, in English

The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth, who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GADA, IA-2A or mIAA) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA SNPs that achieved genome-wide significance for association with T1D in the GWAS meta-analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY-participants carrying high-risk HLA-genotypes, eight SNPs achieved significant association to development of IA using time-to-event analysis (p<0.05), whereof four were significant after adjustment for multiple testing (p<0.0012): rs2476601 in PTPN22 (hazard ratio [HR] 1.54 [95% CI 1.27-1.88]), rs2292239 in ERBB3 (HR 1.33 [95% CI 1.14-1.55]), rs3184504 in SH2B3 (HR 1.38 [95% CI 1.19-1.61]) and rs1004446 in INS (HR 0.77 [0.66-0.90]). These SNPs were also significantly associated with T1D in particular: rs2476601 (HR 2.42 [95% CI 1.70-3.44]). Although genes in the HLA-region remain the most important genetic risk factors for T1D, other non-HLA genetic factors contribute to IA, a first step in the pathogenesis of T1D, and the progression of the disease.

Department/s

  • Diabetes and Celiac Unit
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2015

Language

English

Pages

1818-1829

Publication/Series

Diabetes

Volume

64

Issue

5

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 1939-327X