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Identification of n...
Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort
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- Sharma, Ashok (författare)
- Augusta University
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- Liu, Xiang (författare)
- University of South Florida
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- Hadley, David (författare)
- St George's, University of London
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- Hagopian, William (författare)
- Pacific Northwest Research Institute
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- Chen, Wei Min (författare)
- University of Virginia
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- Onengut-Gumuscu, Suna (författare)
- University of Virginia
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- Törn, Carina (författare)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups
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- Steck, Andrea K. (författare)
- University of Colorado
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- Frohnert, Brigitte I. (författare)
- University of Colorado
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- Rewers, Marian (författare)
- University of Colorado
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- Ziegler, Anette G. (författare)
- Helmholtz Zentrum München,Klinikum rechts der Isar
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- Lernmark, Åke (författare)
- Lund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups
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- Toppari, Jorma (författare)
- Turku University Hospital
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- Krischer, Jeffrey P. (författare)
- University of South Florida
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- Akolkar, Beena (författare)
- National Institute of Diabetes and Digestive and Kidney Diseases
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- Rich, Stephen S. (författare)
- University of Virginia
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- She, Jin Xiong (författare)
- Augusta University
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(creator_code:org_t)
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- Elsevier BV, 2018
- 2018
- Engelska.
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411. ; 89, s. 90-100
- Relaterad länk:
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http://dx.doi.org/10...
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https://www.scienced...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip. Cox proportional hazards analyses were performed to discover the SNPs associated with the risk for IA, T1D, or both. Three regions were associated with the risk of developing any persistent confirmed islet autoantibody: one known region near SH2B3 (HR = 1.35, p = 3.58 × 10-7) with Bonferroni-corrected significance and another known region near PTPN22 (HR = 1.46, p = 2.17 × 10-6) and one novel region near PPIL2 (HR = 2.47, p = 9.64 × 10-7) with suggestive evidence (p < 10-5). Two known regions (PTPN22: p = 2.25 × 10-6, INS; p = 1.32 × 10-7) and one novel region (PXK/PDHB: p = 8.99 × 10-6) were associated with the risk for multiple islet autoantibodies. First appearing islet autoantibodies differ with respect to association. Two regions (INS: p = 5.67 × 10-6 and TTC34/PRDM16: 6.45 × 10-6) were associated if the fist appearing autoantibody was IAA and one region (RBFOX1: p = 8.02 × 10-6) was associated if the first appearing autoantibody was GADA. The analysis of T1D identified one region already known to be associated with T1D (INS: p = 3.13 × 10-7) and three novel regions (RNASET2, PLEKHA1, and PPIL2; 5.42 × 10-6 > p > 2.31 × 10-6). These results suggest that a number of low frequency variants influence the risk of developing IA and/or T1D and these variants can be identified by large prospective cohort studies using a survival analysis approach.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Autoimmune disorder
- Gene mapping
- Susceptibility
- TEDDY study
- Type 1 diabetes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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- Av författaren/redakt...
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Sharma, Ashok
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Liu, Xiang
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Hadley, David
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Hagopian, Willia ...
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Chen, Wei Min
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Onengut-Gumuscu, ...
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visa fler...
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Törn, Carina
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Steck, Andrea K.
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Frohnert, Brigit ...
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Rewers, Marian
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Ziegler, Anette ...
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Lernmark, Åke
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Toppari, Jorma
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Krischer, Jeffre ...
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Akolkar, Beena
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Rich, Stephen S.
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She, Jin Xiong
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visa färre...
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Lunds universitet