Localization of a Type 1 Diabetes Locus in the IL2RA/CD25 Region by Use of Tag Single-Nucleotide Polymorphisms

• Published in: American journal of human genetics Vol. 76; no. 5; pp. 773 - 779
• Main Authors: Vella, Adrian, Cooper, Jason D., Lowe, Christopher E., Walker, Neil, Nutland, Sarah, Widmer, Barry, Jones, Richard, Ring, Susan M., McArdle, Wendy, Pembrey, Marcus E., Strachan, David P., Dunger, David B., Rebecca Twells, C.J., Clayton, David G., Todd, John A.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-05-2005; University of Chicago Press; Cell Press; The American Society of Human Genetics
• Subjects: Biological and medical sciences; Case-Control Studies; Chromosomes; Diabetes; Diabetes Mellitus, Type 1 - genetics; Female; Gene loci; General aspects. Genetic counseling; Genetic Predisposition to Disease; Genomics; Humans; Interleukin-2 Receptor alpha Subunit; Linkage Disequilibrium; Male; Medical genetics; Medical sciences; Odds Ratio; Polymorphism; Polymorphism, Single Nucleotide; Receptors, Interleukin - genetics; Endocrinopathy; Human; Immunopathology; Type 1 diabetes; Use; Autoimmune disease; Genetics; Single nucleotide polymorphism; Localization; Locus
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/429843

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.