Role of type 1 diabetes- Associated snps on risk of autoantibody positivity in the TEDDY study

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

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Abstract

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 (GAD antibody, IA-2A, or micro insulin autoantibodies) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with T1D in the genome-wide association scan meta- Analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY participants carrying highrisk 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.

Original languageEnglish (US)
Pages (from-to)1818-1829
Number of pages12
JournalDiabetes
Volume64
Issue number5
DOIs
StatePublished - May 1 2015

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Type 1 Diabetes Mellitus
Autoantibodies
Single Nucleotide Polymorphism
Genotype
Genome-Wide Association Study
Disease Progression
Meta-Analysis
Parturition
Genome
Insulin
Antibodies
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Törn, C., Hadley, D., Lee, H. S., Hagopian, W., Lernmark, Å., Simell, O., ... Krischer, J. (2015). Role of type 1 diabetes- Associated snps on risk of autoantibody positivity in the TEDDY study. Diabetes, 64(5), 1818-1829. https://doi.org/10.2337/db14-1497

Role of type 1 diabetes- Associated snps on risk of autoantibody positivity in the TEDDY study. / Törn, Carina; Hadley, David; Lee, Hye Seung; Hagopian, William; Lernmark, Åke; Simell, Olli; Rewers, Marian; Ziegler, Anette; Schatz, Desmond; Akolkar, Beena; Onengut-Gumuscu, Suna; Chen, Wei Min; Toppari, Jorma; Mykkänen, Juha; Ilonen, Jorma; Rich, Stephen S.; She, Jin-Xiong; Steck, Andrea K.; Krischer, Jeffrey.

In: Diabetes, Vol. 64, No. 5, 01.05.2015, p. 1818-1829.

Research output: Contribution to journalArticle

Törn, C, Hadley, D, Lee, HS, Hagopian, W, Lernmark, Å, Simell, O, Rewers, M, Ziegler, A, Schatz, D, Akolkar, B, Onengut-Gumuscu, S, Chen, WM, Toppari, J, Mykkänen, J, Ilonen, J, Rich, SS, She, J-X, Steck, AK & Krischer, J 2015, 'Role of type 1 diabetes- Associated snps on risk of autoantibody positivity in the TEDDY study', Diabetes, vol. 64, no. 5, pp. 1818-1829. https://doi.org/10.2337/db14-1497
Törn C, Hadley D, Lee HS, Hagopian W, Lernmark Å, Simell O et al. Role of type 1 diabetes- Associated snps on risk of autoantibody positivity in the TEDDY study. Diabetes. 2015 May 1;64(5):1818-1829. https://doi.org/10.2337/db14-1497
Törn, Carina ; Hadley, David ; Lee, Hye Seung ; Hagopian, William ; Lernmark, Åke ; Simell, Olli ; Rewers, Marian ; Ziegler, Anette ; Schatz, Desmond ; Akolkar, Beena ; Onengut-Gumuscu, Suna ; Chen, Wei Min ; Toppari, Jorma ; Mykkänen, Juha ; Ilonen, Jorma ; Rich, Stephen S. ; She, Jin-Xiong ; Steck, Andrea K. ; Krischer, Jeffrey. / Role of type 1 diabetes- Associated snps on risk of autoantibody positivity in the TEDDY study. In: Diabetes. 2015 ; Vol. 64, No. 5. pp. 1818-1829.
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AU - Simell, Olli

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