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 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2004
|
| _version_ | 1826277149707862016 |
|---|---|
| author | Smyth, D Cooper, J Collins, J Heward, J Franklyn, J Howson, J Vella, A Nutland, S Rance, H Maier, L Barratt, B Guja, C Ionescu-Tîrgoviste, C Savage, D Dunger, D Widmer, B Strachan, D Ring, S Walker, N Clayton, D Twells, R Gough, S Todd, J |
| author_facet | Smyth, D Cooper, J Collins, J Heward, J Franklyn, J Howson, J Vella, A Nutland, S Rance, H Maier, L Barratt, B Guja, C Ionescu-Tîrgoviste, C Savage, D Dunger, D Widmer, B Strachan, D Ring, S Walker, N Clayton, D Twells, R Gough, S Todd, J |
| author_sort | Smyth, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:24:33Z |
| format | Journal article |
| id | oxford-uuid:69e9fb2c-90f7-495e-9827-b845b88ebfec |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:24:33Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:69e9fb2c-90f7-495e-9827-b845b88ebfec2022-03-26T18:54:07ZReplication 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.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:69e9fb2c-90f7-495e-9827-b845b88ebfecEnglishSymplectic Elements at Oxford2004Smyth, DCooper, JCollins, JHeward, JFranklyn, JHowson, JVella, ANutland, SRance, HMaier, LBarratt, BGuja, CIonescu-Tîrgoviste, CSavage, DDunger, DWidmer, BStrachan, DRing, SWalker, NClayton, DTwells, RGough, STodd, JIn 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. |
| spellingShingle | Smyth, D Cooper, J Collins, J Heward, J Franklyn, J Howson, J Vella, A Nutland, S Rance, H Maier, L Barratt, B Guja, C Ionescu-Tîrgoviste, C Savage, D Dunger, D Widmer, B Strachan, D Ring, S Walker, N Clayton, D Twells, R Gough, S Todd, J 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. |
| 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| work_keys_str_mv | AT smythd replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT cooperj replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT collinsj replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT hewardj replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT franklynj replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT howsonj replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT vellaa replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT nutlands replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT ranceh replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT maierl replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT barrattb replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT gujac replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT ionescutirgovistec replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT savaged replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT dungerd replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT widmerb replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT strachand replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT rings replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT walkern replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT claytond replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT twellsr replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT goughs replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus AT toddj replicationofanassociationbetweenthelymphoidtyrosinephosphataselocuslypptpn22withtype1diabetesandevidenceforitsroleasageneralautoimmunitylocus |