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Role of Type 1 Diabetes–Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study
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 de...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407865/ https://www.ncbi.nlm.nih.gov/pubmed/25422107 http://dx.doi.org/10.2337/db14-1497 |
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author | 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 |
author_facet | 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 |
author_sort | Törn, Carina |
collection | PubMed |
description | 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 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. |
format | Online Article Text |
id | pubmed-4407865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-44078652016-05-01 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 Diabetes Genetics/Genomes/Proteomics/Metabolomics 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 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. American Diabetes Association 2015-05 2014-11-24 /pmc/articles/PMC4407865/ /pubmed/25422107 http://dx.doi.org/10.2337/db14-1497 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
spellingShingle | Genetics/Genomes/Proteomics/Metabolomics 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 |
title | Role of Type 1 Diabetes–Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study |
title_full | Role of Type 1 Diabetes–Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study |
title_fullStr | Role of Type 1 Diabetes–Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study |
title_full_unstemmed | Role of Type 1 Diabetes–Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study |
title_short | Role of Type 1 Diabetes–Associated SNPs on Risk of Autoantibody Positivity in the TEDDY Study |
title_sort | role of type 1 diabetes–associated snps on risk of autoantibody positivity in the teddy study |
topic | Genetics/Genomes/Proteomics/Metabolomics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407865/ https://www.ncbi.nlm.nih.gov/pubmed/25422107 http://dx.doi.org/10.2337/db14-1497 |
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