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-Tîrgoviste; David A Savage; David B Dunger; Barry Widmer; David P Strachan; Susan M Ring; Neil Walker; David G Clayton; Rebecca C J Twells; Stephen C L Gough; John A Todd

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-Tîrgoviste, 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

Bristol Medical School (PHS)

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

397 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 x 10(-27)). We also report evidence for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 x 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 language	English
Pages (from-to)	3020-3
Number of pages	4
Journal	Diabetes
Volume	53
Issue number	11
Publication status	Published - Nov 2004

Keywords

Adult
Autoimmunity
Child
Chromosome Mapping
Diabetes Mellitus, Type 1
Female
Genotype
Humans
Male
Nuclear Family
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases
Reference Values
Regression Analysis

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Smyth, D., Cooper, J. D., Collins, J. E., Heward, J. M., Franklyn, J. A., Howson, J. M. M., Vella, A., Nutland, S., Rance, H. E., Maier, L., Barratt, B. J., Guja, C., Ionescu-Tîrgoviste, C., Savage, D. A., Dunger, D. B., Widmer, B., Strachan, D. P., Ring, S. M., Walker, N., ... Todd, J. A. (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, 53(11), 3020-3.

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-Tîrgoviste, 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. 3020-3.

@article{921001c680f14369b9a6408a16e05bf3,

title = "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",

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 x 10(-27)). We also report evidence for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 x 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.",

keywords = "Adult, Autoimmunity, Child, Chromosome Mapping, Diabetes Mellitus, Type 1, Female, Genotype, Humans, Male, Nuclear Family, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Protein Tyrosine Phosphatases, Reference Values, Regression Analysis",

author = "Deborah Smyth and Cooper, {Jason D} and Collins, {Joanne E} and Heward, {Joanne M} and Franklyn, {Jayne A} and Howson, {Joanna M M} and Adrian Vella and Sarah Nutland and Rance, {Helen E} and Lisa Maier and Barratt, {Bryan J} and Cristian Guja and Constantin Ionescu-T{\^i}rgoviste and Savage, {David A} and Dunger, {David B} and Barry Widmer and Strachan, {David P} and Ring, {Susan M} and Neil Walker and Clayton, {David G} and Twells, {Rebecca C J} and Gough, {Stephen C L} and Todd, {John A}",

year = "2004",

month = nov,

language = "English",

volume = "53",

pages = "3020--3",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "11",

}

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-Tîrgoviste, 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. 3020-3.

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-Tîrgoviste, 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. 3020-3.

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

TY - JOUR

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-Tîrgoviste, 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 x 10(-27)). We also report evidence for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 x 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.

AB - 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 x 10(-27)). We also report evidence for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 x 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.

KW - Adult

KW - Autoimmunity

KW - Child

KW - Chromosome Mapping

KW - Diabetes Mellitus, Type 1

KW - Female

KW - Genotype

KW - Humans

KW - Male

KW - Nuclear Family

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 1

KW - Protein Tyrosine Phosphatases

KW - Reference Values

KW - Regression Analysis

M3 - Article (Academic Journal)

C2 - 15504986

VL - 53

SP - 3020

EP - 3023

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -