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

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

301 Citations (Scopus)

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.

Original language	English
Pages (from-to)	773-9
Number of pages	7
Journal	American Journal of Human Genetics
Volume	76
Issue number	5
DOIs	https://doi.org/10.1086/429843
Publication status	Published - 2005

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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), 773-9. https://doi.org/10.1086/429843

@article{ee4ac734ff174306b9dba6feedba9c83,

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.",

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}",

year = "2005",

doi = "10.1086/429843",

language = "English",

volume = "76",

pages = "773--9",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

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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. 773-9. https://doi.org/10.1086/429843

TY - JOUR

T1 - Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms

AU - Vella, Adrian

AU - Cooper, Jason D

AU - Lowe, Christopher E

AU - Walker, Neil

AU - Nutland, Sarah

AU - Widmer, Barry

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

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1086/429843

DO - 10.1086/429843

M3 - Article (Academic Journal)

C2 - 15776395

SN - 0002-9297

VL - 76

SP - 773

EP - 779

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 5

ER -

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

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