rs2476601

Orientation

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Stabilized

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Geno	Mag	Summary
(A;A)	3.2	2x risk of rheumatoid arthritis and other autoimmune diseases
(A;G)	2	Increased Risk of Multiple Autoimmune Disorders
(G;G)	0	Normal risk for autoimmune disorders

Reference

GRCh38 38.1/141

Chromosome

1

Position

113834946

Gene	AP4B1-AS1, PTPN22

is a	snp
is	mentioned by
dbSNP	rs2476601
dbSNP (classic)	rs2476601
ClinGen	rs2476601
ebi	rs2476601
HLI	rs2476601
Exac	rs2476601
Gnomad	rs2476601
Varsome	rs2476601
LitVar	rs2476601
Map	rs2476601
PheGenI	rs2476601
Biobank	rs2476601
1000 genomes	rs2476601
hgdp	rs2476601
ensembl	rs2476601
geneview	rs2476601
scholar	rs2476601
google	rs2476601
pharmgkb	rs2476601
gwascentral	rs2476601
openSNP	rs2476601
23andMe	rs2476601
SNPshot	rs2476601
SNPdbe	rs2476601
MSV3d	rs2476601
GWAS Ctlg	rs2476601

GMAF

0.04224

Max Magnitude

3.2

?	(A;A) (A;G) (G;G)	28

ClinVar
Risk	Rs2476601(G;G)
Alt	Rs2476601(G;G)
Reference	Rs2476601(A;A)
Significance	Other
Disease	Diabetes mellitus Rheumatoid arthritis Systemic lupus erythematosus Hashimoto thyroiditis Addison disease
Variation	info
Gene	PTPN22 AP4B1-AS1
CLNDBN	Diabetes mellitus, insulin-dependent, susceptibility to Rheumatoid arthritis Systemic lupus erythematosus, susceptibility to Hashimoto thyroiditis, susceptibility to Addison disease, susceptibility to
Reversed	0
HGVS	NC_000001.10:g.114377568A\x3d
CLNSRC	OMIM Allelic Variant
CLNACC	RCV000009460.2, RCV000009461.2, RCV000009462.2, RCV000009463.2, RCV000009464.2,

GWAS snp
PMID	[PMID 18587394]
Trait	Crohn's disease
Title	Genome-wide assocation defines more than 30 distinct susceptibility loci for Crohn's disease
Risk Allele	G
P-val	1E-8
Odds Ratio	1.31 [NR]

GWAS snp
PMID	[PMID 17632545]
Trait	Type 1 diabetes
Title	A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene
Risk Allele	A
P-val	9.9999999999999995E-8
Odds Ratio	1.80 [1.44-2.24]

GWAS snp
PMID	[PMID 19430480]
Trait	Type 1 diabetes
Title	Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes
Risk Allele
P-val	9E-85
Odds Ratio	NR NR

GWAS snp
PMID	[PMID 19503088]
Trait	Rheumatoid arthritis
Title	REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis
Risk Allele
P-val	2E-21
Odds Ratio	NR NR

GWAS snp
PMID	[PMID 20410501]
Trait	Vitiligo
Title	Variant of TYR and Autoimmunity Susceptibility Loci in Generalized Vitiligo
Risk Allele	A
P-val	1E-7
Odds Ratio	1.39 [1.23-1.57]

GWAS snp
PMID	[PMID 20453842]
Trait	Rheumatoid arthritis
Title	Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk lock
Risk Allele	A
P-val	9E-74
Odds Ratio	1.94 [1.81-2.08]

GWAS snp
PMID	[PMID 21829393]
Trait
Title	Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases.
Risk Allele	A
P-val	2E-111
Odds Ratio	2.0000 [NR]

GWAS snp
PMID	[PMID 23055271]
Trait	Myasthenia gravis
Title	Risk for myasthenia gravis maps to a (151) Pro→Ala change in TNIP1 and to human leukocyte antigen-B*08.
Risk Allele	A
P-val	8E-10
Odds Ratio	1.71 [1.44-2.02]

GWAS snp
PMID	[PMID 21102463]
Trait	Crohn's disease
Title	Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
Risk Allele	G
P-val	4E-9
Odds Ratio	1.26 [1.17-1.37]

GWAS snp
PMID	[PMID 24390342]
Trait	Rheumatoid arthritis
Title	Genetics of rheumatoid arthritis contributes to biology and drug discovery.
Risk Allele	A
P-val	9E-170
Odds Ratio	1.80 [1.73-1.88]

GWAS snp
PMID	[PMID 24449572]
Trait	Rheumatoid arthritis
Title	Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study.
Risk Allele
P-val	5E-33
Odds Ratio	1.77 [1.61-1.95]

GWAS snp
PMID	[PMID 21156761]
Trait	Rheumatoid arthritis
Title	A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.
Risk Allele
P-val	1E-8
Odds Ratio	NR NR

OMIM	600716
Desc	DIABETES MELLITUS, INSULIN-DEPENDENT, SUSCEPTIBILITY TO
Variant	0001
Related	also

OMIM	240200
Desc	HYPOADRENOCORTICISM, FAMILIAL
Variant
Related	also

OMIM	152700
Desc
Variant
Related	also

OMIM	222100
Desc
Variant
Related	also

This important SNP, located in the PTPN22 gene and also known as R620W, C1858T, or 1858C>T, may influence risk for multiple autoimmune diseases, such as Rheumatoid Arthritis, Type-1 diabetes, Autoimmune thyroiditis, and Systemic lupus erythematosus.

Overview

[PMID 25003765] PTPN22: the archetypal non-HLA autoimmunity gene. A 2014 article explained that "PTPN22 exemplifies a shared autoimmunity gene, affecting the pathogenesis of systemic lupus erythematosus, vasculitis and other autoimmune diseases." They explored "the role of PTPN22 in autoimmune connective tissue disease" and theorized "a number of PTPN22-dependent functional models of the pathogenesis of autoimmune diseases." (Abstract). They explained that "the PTPN22 gene is a major risk factor for autoimmunity." As well, "In addition to autoimmune diseases, PTPN22 1858C>T also affects susceptibility to infectious diseases."

[PMID 15719322] A 2005 study titled "Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes" stated "We report that a recently described functional single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes in these families: T1D, RA, SLE, and Hashimoto's thyroiditis. MS did not show association with the PTPN22 risk allele. These findings suggest a common underlying etiologic pathway for some, but not all, autoimmune disorders, and they suggest that MS may have a pathogenesis that is distinct from RA, SLE, and T1D." (Abstract).

[PMID 22857794] Autoimmunity in primary antibody deficiency is associated with protein tyrosine phosphatase nonreceptor type 22 (PTPN22).

[PMID 20444268] Peripheral blood gene expression patterns discriminate among chronic inflammatory diseases and healthy controls and identify novel targets.

NOTE

Promethease reports for rs2476601 from Trait-o-matic are consistently finding this called as (A;G), while microarray results seem to follow the HapMap predictions. The source of this originates upstream in several different genotype callers:

• maq
• SoapSNP
• AB_SOLiD_SNP_caller
• JW
• NA18507
• SIQ2
• CV
• GSNAP

This is probably triggered by the oddness of this dbSNP entry in which it is a C=>T in NM_012411.2 and a T=>C in NM_015967.3 and/or the fact NT_019273.18 was replaced by NT_032977

Rheumatoid arthritis

[PMID 17554300] A 2007 study titled "Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls" examined approximately 2,000 individuals for each of 7 major diseases and a shared set of approximately 3,000 controls in the British population. They found that in the case of rs2476601, the risk was consistent with previous estimates for RA, approximately OD 1.8, and that "known associations with HLA-DRB1 and PTPN22 explain around 50% of the familial aggregation of RA." They found a correlated marker for RA, rs6679677. In addition, SNP rs11761231 had no effect on risk in males, but in females had an "additive OR for females 1.32"

[PMID 16175503] A 2005 study titled "PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis" found that R620W rs2476601 polymorphism was the most significant SNP in sample set of 37 SNPs. They also found these significant ORs for RA (estimated for the minor allele of each SNP; Table 1):

• rs2476601 1.65 (p=6.6E-04)
• rs974404 1.49 (p=2.4E-05)
• rs2476600 1.49 (p=2.5E-05)
• rs2797416 1.49 (p=2.2E-05)
• rs1310182 1.48 (p=3.2E-05)
• rs2476604 1.48 (p=2.7E-05)
• rs1217420 1.48 (p=2.7E-05) (same)
• rs1217406 1.47 (p=4.6E-05)
• rs12730735 0.65 (reduced risk) (p=2.0E-05)
• rs3789609 0.65 (reduced risk) (p=2.7E-05)
• rs12760457 0.65 (reduced risk) (p=2.0E-05)

However, they found that "R620W by itself does not account for all the association observed between RA and PTPN22 in both sample sets." Further analysis revealed that two of the SNPs were important in relation to rs2476601, namely their SNP "number 27" (rs1310182) and "number 37" (rs3789604, which had OR 1.39 (p=0.0071). It showed that the R620W polymorphism was moderated by other SNPs, one increasing its OR, the other decreasing it..

• In combination, the minor allele of rs3789604 gave an increased OR of 2.53 to minor allele homozygotes and 1.77 to heterozygotes of rs2476601
• In combination, the minor allele of rs1310182 gave a decreased OR of 1.63 to minor allele homozygotes and 1.34 to heterozygotes of rs2476601

[PMID 19357851] No association of PTPN22 gene polymorphism with rheumatoid arthritis in Turkey.

[PMID 15674368] A 2005 study titled "The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-dependent manner but not with HLA-SE status" stated two copies of the PTPN22 R620W allele more than doubled the risk for RF positive RA

[PMID 15934099] A 2005 study titled "Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene" found that "There was a significant association between the PTPN22 SNP and RA (P = 1.8 x 10(-8)) and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected." (Abstract).

[PMID 16490755] A 2006 study titled "Effects of PTPN22 C1858T polymorphism on susceptibility and clinical characteristics of British Caucasian rheumatoid arthritis patients" confirms the association of rs2476601 rheumatoid arthritis

[PMID 17804836]This SNP rs2476601 was confirmed in a 2007 study to be a risk factor for RA

[PMID 20032229] Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms

[PMID 25138370] Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies in HLA-defined subgroups of rheumatoid arthritis

[PMID 21193990] A PTPN22 promoter polymorphism -1123G>C is associated with RA pathogenesis in Chinese.

[PMID 20498205] Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers

[PMID 21965649] Evidence for PTPN2 R620W Polymorphism As the Sole Common Risk Variant for Rheumatoid Arthritis in the 1p13.2 Region

[PMID 22427951] PTPN22.6, a Dominant Negative Isoform of PTPN22 and Potential Biomarker of Rheumatoid Arthritis

[PMID 22632125] Evidence of cis-acting regulatory variation in PTPN22 in patients with rheumatoid arthritis

[PMID 21922340] Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset.

[PMID 22743847] The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico

[PMID 23582631] Pathway analysis of genome-wide association studies on rheumatoid arthritis

[PMID 22328738] Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.

[PMID 22440825] Relationship between area-level socio-economic deprivation and autoantibody status in patients with rheumatoid arthritis: multicentre cross-sectional study.

[PMID 22674012] Association of anti-citrullinated vimentin and anti-citrullinated alpha-enolase antibodies with subsets of rheumatoid arthritis.

[PMID 23223422] Identification of the NF-kappaB activating protein-like locus as a risk locus for rheumatoid arthritis.

[PMID 23350658] Association of PTPN22 rs2476601 and EGFR rs17337023 Gene polymorphisms and rheumatoid arthritis in Zahedan, Southeast Iran.

[PMID 23450725] Susceptibility to childhood-onset rheumatoid arthritis: investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci.

[PMID 23637320] Metaanalysis of the association of smoking and PTPN22 R620W genotype on autoantibody status and radiological erosions in rheumatoid arthritis.

[PMID 24880676] Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis

[PMID 16380915] Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.

[PMID 16945141] Fine mapping of genes within the IDDM8 region in rheumatoid arthritis.

[PMID 17170052] Investigation of genetic variation across the protein tyrosine phosphatase gene in patients with rheumatoid arthritis in the UK.

[PMID 17579671] Association of PTPN22 single nucleotide polymorphism with rheumatoid arthritis but not with allergic asthma.

[PMID 17665434] Association of interleukin-6 and interleukin-10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status.

[PMID 17666451] Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study.

[PMID 18434327] Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility.

[PMID 18462498] Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking.

[PMID 18466461] Meta-genetic association of rheumatoid arthritis and PTPN22 using PedGenie 2.1.

[PMID 18466472] Constructing gene association networks for rheumatoid arthritis using the backward genotype-trait association (BGTA) algorithm.

[PMID 18466483] Modeling of PTPN22 and HLA-DRB1 susceptibility to rheumatoid arthritis.

[PMID 18466513] Evaluating gene x gene and gene x smoking interaction in rheumatoid arthritis using candidate genes in GAW15.

[PMID 18466531] Case-control association analysis of rheumatoid arthritis with candidate genes using related cases.

[PMID 18466535] Modeling the effect of PTPN22 in rheumatoid arthritis.

[PMID 18466554] Analyses of single marker and pairwise effects of candidate loci for rheumatoid arthritis using logistic regression and random forests.

[PMID 18466563] Classification of rheumatoid arthritis status with candidate gene and genome-wide single-nucleotide polymorphisms using random forests.

[PMID 18648537] A large-scale rheumatoid arthritis genetic study identifies association at chromosome 9q33.2.

[PMID 18668548] Genome-wide association study of rheumatoid arthritis in the Spanish population: KLF12 as a risk locus for rheumatoid arthritis susceptibility.

[PMID 18794853] Common variants at CD40 and other loci confer risk of rheumatoid arthritis.

[PMID 18987647] Rheumatoid arthritis: a view of the current genetic landscape.

[PMID 19180477] Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations.

[PMID 19445664] Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls.

[PMID 20017963] Representation of genetic association via attributable familial relative risks in order to identify polymorphisms functionally relevant to rheumatoid arthritis.

[PMID 20017967] Genome-wide association analyses of North American Rheumatoid Arthritis Consortium and Framingham Heart Study data utilizing genome-wide linkage results.

[PMID 20017974] Simultaneous analysis of all single-nucleotide polymorphisms in genome-wide association study of rheumatoid arthritis.

[PMID 20017985] Adjusting for HLA-DRbeta1 in a genome-wide association analysis of rheumatoid arthritis and related biomarkers.

[PMID 20018006] Case-control genome-wide association study of rheumatoid arthritis from Genetic Analysis Workshop 16 using penalized orthogonal-components regression-linear discriminant analysis.

[PMID 20018022] Replication of recently identified associated single-nucleotide polymorphisms from six autoimmune diseases in Genetic Analysis Workshop 16 rheumatoid arthritis data.

[PMID 20018025] Genome-wide analysis of haplotype interaction for the data from the North American Rheumatoid Arthritis Consortium.

[PMID 20018027] Conditional analysis of the major histocompatibility complex in rheumatoid arthritis.

[PMID 20018035] A combinatorial approach for detecting gene-gene interaction using multiple traits of Genetic Analysis Workshop 16 rheumatoid arthritis data.

[PMID 20018053] A genome-wide association scan for rheumatoid arthritis data by Hotelling's T2 tests.

[PMID 20018057] Detecting single-nucleotide polymorphism by single-nucleotide polymorphism interactions in rheumatoid arthritis using a two-step approach with machine learning and a Bayesian threshold least absolute shrinkage and selection operator (LASSO) model.

[PMID 20018062] Identification of genes and haplotypes that predict rheumatoid arthritis using random forests.

[PMID 20018071] Allelic based gene-gene interactions in rheumatoid arthritis.

[PMID 20018074] Identifying rheumatoid arthritis susceptibility genes using high-dimensional methods.

[PMID 20018080] Effects of covariates and interactions on a genome-wide association analysis of rheumatoid arthritis.

[PMID 20353580] Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort.

[PMID 20439292] Genetic variants in the prediction of rheumatoid arthritis.

[PMID 21383967] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

[PMID 21506938] Association of the PTPN22 gene polymorphism with autoantibody positivity in Turkish rheumatoid arthritis patients.

[PMID 21752868] PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort.

[PMID 26547712] Single Nucleotide Polymorphism rs 2476601 of PTPN22 Gene and Susceptibility to Rheumatoid Arthritis in Iranian Population

[PMID 27215233] Association of PTPN22 rs2476601 Polymorphism with Rheumatoid Arthritis and Celiac Disease in Khuzestan Province, Southwestern Iran.

Juvenile idiopathic arthritis

[PMID 15934099] A 2005 study titled "Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene" found that "There was a significant association between the PTPN22 SNP and RA (P = 1.8 x 10(-8)) and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected." (Abstract).

[PMID 22327470] The association between the functional PTPN22 1858 C/T and MIF -173 C/G polymorphisms and juvenile idiopathic arthritis: a meta-analysis.

[PMID 26587490] The Association between PTPN22 Genetic Polymorphism and Juvenile Idiopathic Arthritis (JIA) Susceptibility: An Updated Meta-Analysis

[PMID 20722033] The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1.

[PMID 24160187] Meta-analysis confirms association between TNFA-G238A variant and JIA, and between PTPN22-C1858T variant and oligoarticular, RF-polyarticular and RF-positive polyarticular JIA

[PMID 17000021] No independent role of the -1123 G>C and+2740 A>G variants in the association of PTPN22 with type 1 diabetes and juvenile idiopathic arthritis in two Caucasian populations.

[PMID 23777930] Investigation of juvenile idiopathic arthritis susceptibility loci: results from a Greek population.

[PMID 27107590] Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population.

[PMID 18821667] The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients.

[PMID 19210888] Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients.

[PMID 25781893] STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C Polymorphisms Influence the Risk of Developing Juvenile Idiopathic Arthritis in Han Chinese Patients

Type 1 Diabetes

[PMID 18776148] Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis: from epidemiology to mechanisms.

[PMID 17334650] A type 1 diabetes subgroup with a female bias is characterised by failure in tolerance to thyroid peroxidase at an early age and a strong association with the cytotoxic T-lymphocyte-associated antigen-4 gene.

[PMID 16470599] A 2006 study was titled "Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations"

[PMID 25005490] The association of PTPN22 rs2476601 polymorphism and CTLA-4 rs231775 polymorphism with LADA risks: a systematic review and meta-analysis. LADA = latent autoimmune diabetes in adults. Similar to Type 1 Diabetes.

[PMID 17554260] In a 2007 study of >6,000 controls and 6,000 patients, the heterozygote odds ratio for type-1 diabetes for this SNP was recalculated to be 1.98 (CI 1.82-2.15).

[PMID 17934143]] Confirms association of rs2476601 with type-1 diabetes in a Sardinian population of 490 sporadic patients (794 families).

[PMID 18305142] rs2476601(A) has a higher relative risk in type-1 diabetes cases carrying lower risk HLA class II genotypes than in those carrying higher risk ones (p=1.36x10^-4 in a test of interaction).

[PMID 19956106] Analysis of 19 genes for association with type I diabetes in the Type I Diabetes Genetics Consortium families

[PMID 19956096] rs2476601 T allele (R620W) defines high-risk PTPN22 type I diabetes-associated haplotypes with preliminary evidence for an additional protective haplotype

[PMID 24103478] Contribution of PTPN22, CD28, CTLA-4 and ZAP-70 variants to the risk of type 1 diabetes in Tunisians

[PMID 23054006] Meta-analysis of the family-based association between the PTPN22 C1858T polymorphism and type 1 diabetes.

[PMID 24913133] Association of PTPN22+1858C/T polymorphism with Type 1 diabetes in the North Indian population

[PMID 17000021] No independent role of the -1123 G>C and+2740 A>G variants in the association of PTPN22 with type 1 diabetes and juvenile idiopathic arthritis in two Caucasian populations.

[PMID 17606874] Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes.

[PMID 17683561] The TCF7L2 locus and type 1 diabetes.

[PMID 18292987] Joint effects of HLA, INS, PTPN22 and CTLA4 genes on the risk of type 1 diabetes.

[PMID 18310307] Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes.

[PMID 18556337] Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1).

[PMID 18978792] Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci.

[PMID 19073967] Shared and distinct genetic variants in type 1 diabetes and celiac disease.

[PMID 19119414] IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production.

[PMID 19188433] Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes?

[PMID 19956109] The Type I Diabetes Genetics Consortium 'Rapid Response' family-based candidate gene study: strategy, genes selection, and main outcome.

[PMID 20089178] Allelic variants in the PHTF1-PTPN22, C12orf30 and CD226 regions as candidate susceptibility factors for the type 1 diabetes in the Estonian population.

[PMID 26074154] Non-HLA gene effects on the disease process of type 1 diabetes: From HLA susceptibility to overt disease.

[PMID 28646072] Genetic and Environmental Interactions Modify the Risk of Diabetes-Related Autoimmunity by 6 Years of Age: The TEDDY Study.

Lupus (Systemic Lupus Erythematosus; SLE)

[PMID 16052172] A 2005 study titled "The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1" in addition to SLE results also "found evidence of a genetic association between PTPN22 and renal disorder" (Abstract)

[PMID 19210878] Women with (T;T) and (C;T) genotypes displayed a 2x increased risk of systemic lupus erythematosus (95% CI=1.324 - 3.070, P=0.0014)

[PMID 18075792] PTPN22: its role in SLE and autoimmunity.

[PMID 23950893] PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

[PMID 21384170] No association of PTPN22 R620 W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus

[PMID 21968398] TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey

[PMID 18759295] The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-alpha activity and low tumor necrosis factor alpha levels in patients with lupus.

[PMID 19591781] The search for lupus biomarkers.

[PMID 19838195] A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.

[PMID 21078766] The association between the PTPN22 C1858T polymorphism and systemic lupus erythematosus: a meta-analysis update.

[PMID 21379322] Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes.

[PMID 21408207] Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production.

[PMID 26092158] IRF5, PTPN22, CD28, IL2RA, KIF5A, BLK and TNFAIP3 genes polymorphisms and lupus susceptibility in a cohort from the Egypt Delta; relation to other ethnic groups

Systemic sclerosis

[PMID 21688149] Meta-analysis across 12 studies, totaling 4,300+ patients, concludes that there is an association between the rs2476601(A) allele and risk for systemic sclerosis, with an odds ratio of 1.169 (CI: 1.05 - 1.3, p = 0.004).

[PMID 17133608] associations of rs2476601 in PTPN22 R620W single-nucleotide polymorphism (SNP) with systemic sclerosis (SSc) or with anticentromere antibody (ACA)-positive or anti-topoisomerase I (anti-topo I) antibody-positive SSc, in a case-control study of US white, black, Hispanic, and Choctaw Indian individuals.

[PMID 18576360] rs2476601(A) allele is associated with (slightly) increased risk for systemic sclerosis in European Caucasians.

[PMID 21131644] Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

[PMID 16464986] Lack of association between the protein tyrosine phosphatase non-receptor 22 (PTPN22)*620W allele and systemic sclerosis in the French Caucasian population.

[PMID 19923204] Genetic background of systemic sclerosis: autoimmune genes take centre stage.

Vasculitis, arteritis

[PMID 19951419] Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis

[PMID 22696186] The protein tyrosine phosphatase nonreceptor 22 C1858T polymorphism and vasculitis: a meta-analysis

[PMID 20236493] The contribution of genetic variation and infection to the pathogenesis of ANCA-associated systemic vasculitis.

[PMID 23946333] Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis

[PMID 18375974] PTPN22 gene polymorphism in Takayasu's arteritis.

Autoimmune thyroiditis

[PMID 22493691] Novel associations for hypothyroidism include known autoimmune risk loci.

[PMID 20615141] Association of the Protein Tyrosine Phosphatase Nonreceptor 22 Haplotypes with Autoimmune Thyroid Disease in the Japanese Population

[PMID 22069277] Susceptibility influence of a PTPN22 haplotype with thyroid autoimmunity in Koreans

[PMID 23463390] Variants in PTPN22 and SMOC2 genes and the risk of thyroid disease in the Jordanian Arab population.

[PMID 18578611]] rs2476601 is not associated with Graves' disease in a study of Japanese patients.

[PMID 17148556] Association of PTPN22 haplotypes with Graves' disease.

[PMID 24386393] Genetic Heterogeneity of Susceptibility Gene in Different Ethnic Populations: Refining Association Study of PTPN22 for Graves' Disease in a Chinese Han Population

Crohn's disease, Ulcerative colitis, and Inflammatory bowel disease

[PMID 21287672] Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis

[PMID 23974994] Replication Study of Ulcerative Colitis Risk Loci in a Lithuanian-Latvian Case-Control Sample

[PMID 21304977] An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.

[PMID 19068216] Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship.

[PMID 16185327] A 2005 study was titled "The functional genetic variation in the PTPN22 gene has a negligible effect on the susceptibility to develop inflammatory bowel disease."

[PMID 24971461] Polymorphisms in the Inflammatory Pathway Genes TLR2, TLR4, TLR9, LY96, NFKBIA, NFKB1, TNFA, TNFRSF1A, IL6R, IL10, IL23R, PTPN22, and PPARG Are Associated with Susceptibility of Inflammatory Bowel Disease in a Danish Cohort

[PMID 20403149] PTPN2 but not PTPN22 is associated with Crohn's disease in a New Zealand population.

Other diseases

[PMID 17660222] studied ~300 UK patients with Behcet's disease and found that the R620W allele (i.e. rs2476601(A)) appeared to provide protection from Behcet's disease. The odds ratio for protection was calculated to be 2.4 (CI: 1.2 - 4.7).

[PMID 18200060] PTPN22 1858T allele had an allelic odds ratio (OR) of 2.16 for generalized vitiligo and a genotypic OR of 2.35 as C/T heterozygotes. Similarly, individuals carrying the PTPN22 1858T allele had an allelic OR of 2.05 for the expanded autoimmunity phenotype, and a genotypic OR of 2.19 for C/T heterozygotes.

[PMID 18301444] In study of 332 Norwegian patients plus a meta-analysis, the rs2476601(A) allele was linked to autoimmune Addison's disease (p=0.003)

[PMID 19780033] Association of a functional polymorphism of PTPN22 encoding a lymphoid protein phosphatase in bilateral Meniere's disease

[PMID 21410964] Association between the PTPN22 +1858 C/T polymorphism and psoriatic arthritis

[PMID 21724255] Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid leukemia

[PMID 22396730] No Association of PTPN22 Polymorphisms with Susceptibility to Ocular Behcet's Disease in Two Chinese Han Populations

[PMID 22197427] PTPN22 and myasthenia gravis: replication in an Italian population and meta-analysis of literature data

[PMID 23944755] The impact of CTLA4 and PTPN22 genes polymorphisms on long-term renal allograft function and transplant outcomes

[PMID 25073032] Association Between a Gain-of-Function Variant of PTPN22 and Rejection in Liver Transplantation

[PMID 17868256] PTPN22 gene polymorphism in Behcet's disease.

[PMID 18341666] Polymorphisms in the PTPN22 region are associated with psoriasis of early onset.

[PMID 18456185] Genetics and genomics of primary biliary cirrhosis.

[PMID 18535005] The search for genes contributing to endometriosis risk.

[PMID 18710467] The tryptophan 620 allele of the lymphoid tyrosine phosphatase (PTPN22) gene predisposes to autoimmune Addison's disease.

[PMID 19180256] Genotype analysis of polymorphisms in autoimmune susceptibility genes, CTLA-4 and PTPN22, in an acute anterior uveitis cohort.

[PMID 19503742] Evaluation of PTPN22 polymorphisms and Vogt-Koyanagi-Harada disease in Japanese patients.

[PMID 20696024] PTPN22 polymorphism is related to autoimmune disease risk in patients with Turner syndrome.

[PMID 21570397] Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles.

[PMID 22210423] Lack of association of the rs2476601 PTPN22 gene polymorphism with transplanted kidney function.

[PMID 22511809] Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study.

[PMID 22544573] PTPN22 C1858T and the risk of psoriasis: a meta-analysis.

[PMID 25119822] The association of PTPN22 R620W polymorphism is stronger with late-onset AChR-myasthenia gravis in Turkey

[PMID 26640579] Association between PTPN22 C1858T polymorphism and alopecia areata risk.

PTPN22 in genetics research

[PMID 20522204] PTPN22 gene regulates natural killer cell proliferation during in vitro expansion

[PMID 19474294] Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.

[PMID 20166877] Allele and haplotype frequency distribution in PTPN22 gene across variable ethnic groups: Implications for genetic association studies for autoimmune diseases.

[PMID 17044734] European population substructure: clustering of northern and southern populations.

[PMID 18248681] Prevalence of common disease-associated variants in Asian Indians.

[PMID 18466529] Comparing strategies for evaluation of candidate genes in case-control studies using family data.

[PMID 19098027] SNPnexus: a web database for functional annotation of newly discovered and public domain single nucleotide polymorphisms.

[PMID 19408013] Strategies and issues in the detection of pathway enrichment in genome-wide association studies.

[PMID 19569043] Genome-wide association studies and the genetic dissection of complex traits.

[PMID 19682379] TagSNP transferability and relative loss of variability prediction from HapMap to an admixed population.

[PMID 19776214] SimCT: a generic tool to visualize ontology-based relationships for biological objects.

[PMID 19924720] Analysis of multiple phenotypes.

[PMID 19956101] Overview of the Rapid Response data.

[PMID 20017996] Effect of population stratification on the identification of significant single-nucleotide polymorphisms in genome-wide association studies.

[PMID 20018016] Application of seventeen two-locus models in genome-wide association studies by two-stage strategy.

[PMID 20018019] Two-stage joint selection method to identify candidate markers from genome-wide association studies.

[PMID 20018042] Assessment of genotype imputation methods.

[PMID 20018049] Evaluation of an optimal receiver operating characteristic procedure.

[PMID 20018054] Predictive modeling in case-control single-nucleotide polymorphism studies in the presence of population stratification: a case study using Genetic Analysis Workshop 16 Problem 1 dataset.

[PMID 20018090] Comparative analysis of different approaches for dealing with candidate regions in the context of a genome-wide association study.

[PMID 29409002] PTPN22 and CTLA-4 Polymorphisms are Associated with Polyglandular Autoimmunity.

[PMID 29967194] Systematic approach demonstrates enrichment of multiple interactions between non-HLA risk variants and HLA-DRB1 risk alleles in rheumatoid arthritis.

[PMID 29973096] Analysis of chosen polymorphisms rs2476601 a/G - PTPN22, rs1990760 C/T - IFIH1, rs179247 a/G - TSHR in pathogenesis of autoimmune thyroid diseases in children.

[PMID 29979892] Genetic variant association of PTPN22, CTLA4, IL2RA, as well as HLA frequencies in susceptibility to alopecia areata.

[PMID 30008646] Association of PTPN22 gene polymorphism with non-segmental vitiligo in South Indian Tamils.

[PMID 30208882] Genetically determined high activities of the TNF-alpha, IL23/IL17, and NFkB pathways were associated with increased risk of ankylosing spondylitis.

[PMID 30636557] Single Nucleotide Polymorphisms of PTPN22 Gene in Iranian Patients with Ulcerative Colitis.

[PMID 30675352] Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy.

[PMID 30705675] The Autoimmune-Associated Single Nucleotide Polymorphism Within PTPN22 Correlates With Clinical Outcome After Lung Transplantation.

[PMID 31032751] Genetic Alleles Associated with SLE Susceptibility and Clinical Manifestations in Hispanic Patients from the Dominican Republic.

[PMID 31096440] The association between rs2476601 polymorphism in PTPN22 gene and risk of alopecia areata: A meta-analysis of case-control studies.

[PMID 32328064] Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset.

[PMID 32333475] PTPN22 gene polymorphism and susceptibility to Rheumatoid arthritis (RA): Updated systematic review and meta-analysis.

[PMID 33059697] rs2476601 in PTPN22 gene in rheumatoid arthritis and periodontitis-a possible interface?