title: Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms.
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.
authors.affiliation: 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.
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Lowe
authors.forename: Neil
authors.initials: N
authors.lastname: Walker
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Barry
authors.initials: B
authors.lastname: Widmer
authors.forename: Richard
authors.initials: R
authors.lastname: Jones
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Wendy
authors.initials: W
authors.lastname: McArdle
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Pembrey
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
authors.forename: Rebecca C J
authors.initials: RC
authors.lastname: Twells
authors.forename: David G
authors.initials: DG
authors.lastname: Clayton
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D015810:Linkage Disequilibrium; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin