Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/121325
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Type: | Journal article |
Title: | Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes |
Author: | Howson, J.M.M. Cooper, J.D. Smyth, D.J. Walker, N.M. Stevens, H. She, J.-X. Eisenbarth, G.S. Rewers, M. Todd, J.A. Akolkar, B. Concannon, P. Erlich, H.A. Julier, C. Morahan, G. Nerup, J. Nierras, C. Pociot, F. Rich, S.S. Type 1 Diabetes Genetics Consortium, |
Citation: | Diabetes, 2012; 61(11):3012-3017 |
Publisher: | American Diabetes Association |
Issue Date: | 2012 |
ISSN: | 0012-1797 1939-327X |
Statement of Responsibility: | Joanna M.M. Howson, Jason D. Cooper, Deborah J. Smyth, Neil M. Walker, Helen Stevens ... Jennifer J Couper ... et al. |
Abstract: | The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10⁻⁶ and 2.5 × 10⁻⁵, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 × 10⁻⁵). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. |
Keywords: | Polymorphism, Single Nucleotide |
Rights: | © 2012 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. See http://creativecommons.org/licenses/by -nc-nd/3.0/ for details. |
DOI: | 10.2337/db11-1694 |
Published version: | http://dx.doi.org/10.2337/db11-1694 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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hdl_121325.pdf | Published version | 89.72 kB | Adobe PDF | View/Open |
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