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Törn, C.* ; Hadley, D.* ; Lee, H.S.* ; Hagopian, W.* ; Lernmark, A.* ; Simell, O.* ; Rewers, M.* ; Ziegler, A.-G. ; Schatz, D.* ; Akolkar, B.* ; Onengut-Gumuscu, S.* ; Chen, W.M.* ; Toppari, J.* ; Mykkänen, J.* ; Ilonen, J.* ; Rich, S.S.* ; She, J.X.* ; Steck, A.K.* ; Krischer, J.* ; TEDDY Study Group (Beyerlein, A. ; Bonifacio, E. ; Hummel, M. ; Hummel, S. ; Foterek, K. ; Kersting, M. ; Knopff, A. ; Koletzko, S. ; Peplow, C. ; Roth, R. ; Stock, J. ; Strauss, E. ; Warncke, K. ; Winkler, C.)

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

Diabetes 64, 1818-1829 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Tyrosine-phosphatase Ptpn22; Antibody Standardization Program; Glutamic-acid Decarboxylase; Genome-wide Association; Islet Autoimmunity; Population; Gene; Polymorphism; Assays; Locus
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Journal Diabetes
Quellenangaben Volume: 64, Issue: 5, Pages: 1818-1829 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute of Diabetes and Obesity (IDO)
Institute for Pancreatic Beta Cell Research (IPI)