Advanced

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

Törn, Carina LU ; Hadley, David; Lee, Hye-Seung; Hagopian, William; Lernmark, Åke LU ; Simell, Olli; Rewers, Marian; Ziegler, Anette; Schatz, Desmond and Akolkar, Beena, et al. (2015) In Diabetes 64(5). p.1818-1829
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 (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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
64
issue
5
pages
1818 - 1829
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:25422107
  • wos:000353431200037
  • scopus:84981556018
ISSN
1939-327X
DOI
10.2337/db14-1497
language
English
LU publication?
yes
id
50bd4790-3f30-42b0-b1f8-c5b6ba382042 (old id 4816122)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25422107?dopt=Abstract
date added to LUP
2014-12-03 18:05:25
date last changed
2017-11-05 03:26:32
@article{50bd4790-3f30-42b0-b1f8-c5b6ba382042,
  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 (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&lt;0.05), whereof four were significant after adjustment for multiple testing (p&lt;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.},
  author       = {Törn, Carina and Hadley, David and Lee, Hye-Seung and Hagopian, William and Lernmark, Åke and Simell, Olli and Rewers, Marian and Ziegler, Anette and Schatz, Desmond and Akolkar, Beena and Onengut-Gumuscu, Suna and Chen, Wei-Min and Toppari, Jorma and Mykkänen, Juha and Ilonen, Jorma and Rich, Stephen S and She, Jin-Xiong and Steck, Andrea K and Krischer, Jeffrey},
  issn         = {1939-327X},
  language     = {eng},
  number       = {5},
  pages        = {1818--1829},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Role of Type 1 diabetes associated SNPs on risk of autoantibody positivity in the TEDDY Study.},
  url          = {http://dx.doi.org/10.2337/db14-1497},
  volume       = {64},
  year         = {2015},
}