Copyright © 2005 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 76, Issue 5, 773-779, 1 May 2005
doi:10.1086/429843
Localization of a Type 1 Diabetes Locus in the IL2RA/CD25 Region by Use of Tag Single-Nucleotide Polymorphisms
Adrian Vella1, Jason D. Cooper1, Christopher E. Lowe1, Neil Walker1, Sarah Nutland1, Barry Widmer2, Richard Jones3, Susan M. Ring3, Wendy McArdle3, Marcus E. Pembrey3, 4, David P. Strachan5, David B. Dunger2, C.J. Rebecca Twells1, David G. Clayton1 and John A. Todd1, 
, 
1 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, United Kingdom
2 Department of Paediatrics, Addenbrooke’s Hospital, University of Cambridge, Cambridge, United Kingdom
3 Department of Community-Based Medicine, Bristol University, Bristol, United Kingdom
4 Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London
5 Department of Community Health Sciences, St. George’s Hospital Medical School, London
Address for correspondence and reprints: Prof. John A. Todd, Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2XY, United KingdomAbstract
As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2Rα) of the high-affinity interleukin-2 (IL-2) receptor complex. We employed a tag single-nucleotide polymorphism (tag SNP) approach in large T1D sample collections consisting of 7,457 cases and controls and 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. We found strong statistical evidence in the case-control collection (P=6.5×10−8) for a T1D locus in the CD25 region of chromosome 10p15 and replicated the association in the family collection (P=7.3×10−3; combined P=1.3×10−10). These results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region.
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