Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus

Deborah Smyth, Jason D. Cooper, Joanne E. Collins, Joanne M. Heward, Jayne A. Franklyn, Joanna M M Howson, Adrian Vella, Sarah Nutland, Helen E. Rance, Lisa Maier, Bryan J. Barratt, Cristian Guja, Constantin Ionescu-Tîrgovişte, David A. Savage, David B. Dunger, Barry Widmer, David P. Strachan, Susan M. Ring, Neil Walker, David G. ClaytonRebecca C J Twells, Stephen C L Gough, John A. Todd

Research output: Contribution to journalArticle

384 Citations (Scopus)

Abstract

In the genetic analysis of common, multifactorial diseases, such as type 1 diabetes, true positive irrefutable linkage and association results have been rare to date. Recently, it has been reported that a single nucleotide polymorphism (SNP), 1858C>T, in the gene PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which has been shown to be a negative regulator of T-cell activation, is associated with an increased risk of type 1 diabetes. Here, we have replicated these findings in 1,388 type 1 diabetic families and in a collection of 1,599 case and 1,718 control subjects, confirming the association of the PTPN22 locus with type 1 diabetes (family-based relative risk (RR) 1.67 [95% CI 1.46-1.91], and case-control odds ratio (OR) 1.78 [95% CI 1.54-2.06]; overall P = 6.02 × 10-27). We also report evidence for an association of Trp620 with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 × 10-4; OR 1.43 [95% CI 1.17-1.76]). Taken together, these results indicate a more general association of the PTPN22 locus with autoimmune disease.

Original languageEnglish (US)
Pages (from-to)3020-3023
Number of pages4
JournalDiabetes
Volume53
Issue number11
DOIs
StatePublished - Nov 2004
Externally publishedYes

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Non-Receptor Type 22 Protein Tyrosine Phosphatase
Autoimmunity
Type 1 Diabetes Mellitus
Tyrosine
Odds Ratio
Protein Tyrosine Phosphatases
Graves Disease
Autoimmune Diseases
Single Nucleotide Polymorphism
T-Lymphocytes
Genes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. / Smyth, Deborah; Cooper, Jason D.; Collins, Joanne E.; Heward, Joanne M.; Franklyn, Jayne A.; Howson, Joanna M M; Vella, Adrian; Nutland, Sarah; Rance, Helen E.; Maier, Lisa; Barratt, Bryan J.; Guja, Cristian; Ionescu-Tîrgovişte, Constantin; Savage, David A.; Dunger, David B.; Widmer, Barry; Strachan, David P.; Ring, Susan M.; Walker, Neil; Clayton, David G.; Twells, Rebecca C J; Gough, Stephen C L; Todd, John A.

In: Diabetes, Vol. 53, No. 11, 11.2004, p. 3020-3023.

Research output: Contribution to journalArticle

Smyth, D, Cooper, JD, Collins, JE, Heward, JM, Franklyn, JA, Howson, JMM, Vella, A, Nutland, S, Rance, HE, Maier, L, Barratt, BJ, Guja, C, Ionescu-Tîrgovişte, C, Savage, DA, Dunger, DB, Widmer, B, Strachan, DP, Ring, SM, Walker, N, Clayton, DG, Twells, RCJ, Gough, SCL & Todd, JA 2004, 'Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus', Diabetes, vol. 53, no. 11, pp. 3020-3023. https://doi.org/10.2337/diabetes.53.11.3020
Smyth, Deborah ; Cooper, Jason D. ; Collins, Joanne E. ; Heward, Joanne M. ; Franklyn, Jayne A. ; Howson, Joanna M M ; Vella, Adrian ; Nutland, Sarah ; Rance, Helen E. ; Maier, Lisa ; Barratt, Bryan J. ; Guja, Cristian ; Ionescu-Tîrgovişte, Constantin ; Savage, David A. ; Dunger, David B. ; Widmer, Barry ; Strachan, David P. ; Ring, Susan M. ; Walker, Neil ; Clayton, David G. ; Twells, Rebecca C J ; Gough, Stephen C L ; Todd, John A. / Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. In: Diabetes. 2004 ; Vol. 53, No. 11. pp. 3020-3023.
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abstract = "In the genetic analysis of common, multifactorial diseases, such as type 1 diabetes, true positive irrefutable linkage and association results have been rare to date. Recently, it has been reported that a single nucleotide polymorphism (SNP), 1858C>T, in the gene PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which has been shown to be a negative regulator of T-cell activation, is associated with an increased risk of type 1 diabetes. Here, we have replicated these findings in 1,388 type 1 diabetic families and in a collection of 1,599 case and 1,718 control subjects, confirming the association of the PTPN22 locus with type 1 diabetes (family-based relative risk (RR) 1.67 [95{\%} CI 1.46-1.91], and case-control odds ratio (OR) 1.78 [95{\%} CI 1.54-2.06]; overall P = 6.02 × 10-27). We also report evidence for an association of Trp620 with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 × 10-4; OR 1.43 [95{\%} CI 1.17-1.76]). Taken together, these results indicate a more general association of the PTPN22 locus with autoimmune disease.",
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T1 - Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus

AU - Smyth, Deborah

AU - Cooper, Jason D.

AU - Collins, Joanne E.

AU - Heward, Joanne M.

AU - Franklyn, Jayne A.

AU - Howson, Joanna M M

AU - Vella, Adrian

AU - Nutland, Sarah

AU - Rance, Helen E.

AU - Maier, Lisa

AU - Barratt, Bryan J.

AU - Guja, Cristian

AU - Ionescu-Tîrgovişte, Constantin

AU - Savage, David A.

AU - Dunger, David B.

AU - Widmer, Barry

AU - Strachan, David P.

AU - Ring, Susan M.

AU - Walker, Neil

AU - Clayton, David G.

AU - Twells, Rebecca C J

AU - Gough, Stephen C L

AU - Todd, John A.

PY - 2004/11

Y1 - 2004/11

N2 - In the genetic analysis of common, multifactorial diseases, such as type 1 diabetes, true positive irrefutable linkage and association results have been rare to date. Recently, it has been reported that a single nucleotide polymorphism (SNP), 1858C>T, in the gene PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which has been shown to be a negative regulator of T-cell activation, is associated with an increased risk of type 1 diabetes. Here, we have replicated these findings in 1,388 type 1 diabetic families and in a collection of 1,599 case and 1,718 control subjects, confirming the association of the PTPN22 locus with type 1 diabetes (family-based relative risk (RR) 1.67 [95% CI 1.46-1.91], and case-control odds ratio (OR) 1.78 [95% CI 1.54-2.06]; overall P = 6.02 × 10-27). We also report evidence for an association of Trp620 with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 × 10-4; OR 1.43 [95% CI 1.17-1.76]). Taken together, these results indicate a more general association of the PTPN22 locus with autoimmune disease.

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