Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms.
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.
Vella
Adrian
A
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.
Cooper
Jason D
JD
Lowe
Christopher E
CE
Walker
Neil
N
Nutland
Sarah
S
Widmer
Barry
B
Jones
Richard
R
Ring
Susan M
SM
McArdle
Wendy
W
Pembrey
Marcus E
ME
Strachan
David P
DP
Dunger
David B
DB
Twells
Rebecca C J
RC
Clayton
David G
DG
Todd
John A
JA
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*
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin