Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms

  • Am J Hum Genet. 2005 May;76(5):773-9. doi: 10.1086/429843.
Adrian Vella  1 ,  Jason D Cooper ,  Christopher E Lowe ,  Neil Walker ,  Sarah Nutland ,  Barry Widmer ,  Richard Jones ,  Susan M Ring ,  Wendy McArdle ,  Marcus E Pembrey ,  David P Strachan ,  David B Dunger ,  Rebecca C J Twells ,  David G Clayton ,  John A Todd
Affiliations
  • 1. Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Wellcome Trust/Medical Research Council Building, Addenbrooke's Hospital, Cambridge, United Kingdom.
PMID: 15776395 DOI: 10.1086/429843
Abstract

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-2R Alpha) 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=6.5x10(-8)) for a T1D locus in the CD25 region of chromosome 10p15 and replicated the association in the family collection (P=7.3x10(-3); combined P=1.3x10(-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.