Role of Type 1 diabetes associated SNPs on risk of autoantibody positivity in the TEDDY Study.
(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)
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https://lup.lub.lu.se/record/4816122
- author
- organization
- publishing date
- 2015
- 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
- pmid:25422107
- 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
- 2016-04-01 11:14:40
- date last changed
- 2022-04-28 08:17:55
@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<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.}}, 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}}, doi = {{10.2337/db14-1497}}, volume = {{64}}, year = {{2015}}, }