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

Adrian Vella; 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

doi:10.1086/429843

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

Adrian Vella, 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

Endocrinology, Diabetes, Metabolism, and Nutrition

Research output: Contribution to journal › Article › peer-review

277 Scopus citations

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-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.

Original language	English (US)
Pages (from-to)	773-779
Number of pages	7
Journal	American journal of human genetics
Volume	76
Issue number	5
DOIs	https://doi.org/10.1086/429843
State	Published - May 2005

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1086/429843

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Vella, A., Cooper, J. D., Lowe, C. E., Walker, N., Nutland, S., Widmer, B., Jones, R., Ring, S. M., McArdle, W., Pembrey, M. E., Strachan, D. P., Dunger, D. B., Twells, R. C. J., Clayton, D. G., & Todd, J. A. (2005). Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. American journal of human genetics, 76(5), 773-779. https://doi.org/10.1086/429843

Vella, A, Cooper, JD, Lowe, CE, Walker, N, Nutland, S, Widmer, B, Jones, R, Ring, SM, McArdle, W, Pembrey, ME, Strachan, DP, Dunger, DB, Twells, RCJ, Clayton, DG & Todd, JA 2005, 'Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms', American journal of human genetics, vol. 76, no. 5, pp. 773-779. https://doi.org/10.1086/429843

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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-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.",

author = "Adrian Vella and Cooper, {Jason D.} and Lowe, {Christopher E.} and Neil Walker and Sarah Nutland and Barry Widmer and Richard Jones and Ring, {Susan M.} and Wendy McArdle and Pembrey, {Marcus E.} and Strachan, {David P.} and Dunger, {David B.} and Twells, {Rebecca C.J.} and Clayton, {David G.} and Todd, {John A.}",

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AU - Jones, Richard

AU - Ring, Susan M.

AU - McArdle, Wendy

AU - Pembrey, Marcus E.

AU - Strachan, David P.

AU - Dunger, David B.

AU - Twells, Rebecca C.J.

AU - Clayton, David G.

AU - Todd, John A.

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

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