{{Rsnum
|rsid=7574865
|Gene=STAT4
|Chromosome=2
|position=191099907
|Orientation=plus
|GMAF=0.2493
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
|Gene_s=STAT4
}}{{ population diversity
| geno1=(G;G)
| geno2=(G;T)
| geno3=(T;T)
| CEU | 60.2 | 33.6 | 6.2
| HCB | 40.9 | 47.0 | 12.1
| JPT | 42.7 | 43.6 | 13.6
| YRI | 75.2 | 21.4 | 3.4
| ASW | 75.0 | 21.4 | 3.6
| CHB | 40.9 | 47.0 | 12.1
| CHD | 33.0 | 54.7 | 12.3
| GIH | 40.0 | 51.0 | 9.0
| LWK | 73.8 | 23.4 | 2.8
| MEX | 36.8 | 45.6 | 17.5
| MKK | 73.5 | 25.2 | 1.3
| TSI | 63.4 | 29.7 | 6.9
| HapMapRevision=28
}}[[rs7574865]], a SNP in the third intron of the [[STAT4]] gene, has been reported in a large study of Swedes to be associated with both [[rheumatoid arthritis]] (RA) and lupus ([[SLE]]). Among other studies, it has been confirmed in a meta-analysis of 8 studies totaling 7,381 patients and over 10,000 controls from both European and Asian populations.{{PMID|20169389}}

The risk allele (oriented to the dbSNP entry) is (T); the odds ratio associated the presence of a risk allele was 1.3 for [[rheumatoid arthritis]] and 1.55 for lupus ([[SLE]]). The paper states that, "Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis." {{PMID|17804842|OA=1
}}

A study of 124 Caucasian patients with primary [[Sjögren's syndrome]], an autoimmune disease related to RA and SLE, also found the [[rs7574865]](T) allele to be associated with higher risk for this condition (p=0.01). The GT genotype is associated with 1.42x and the TT with 2.28x odds. {{PMID|18273036}}

{{PMID|18516230|OA=1
}} associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10(-19)), nephritis (MAF = 34.3%, OR = 1.80, p<10(-11)), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10(-13))

{{PMID|18576330}} The combined ORs for RA and SLE, respectively, were 1.27 (P = 8.4 x 10(-9)) and 1.61 (P = 2.1 x 10(-11)) for allele frequency distribution; these ORs in the Japanese were quite similar to those previously observed in the Caucasian population

{{PMID|18576336}} RA risk associated with [[rs7574865]](T) allele was also found in studies of 923 Spanish, 273 Swedish, and 876 Dutch patients.

{{PMID|18703106}} The [[rs7574865]](T) allele is associated with increased risk for [[type-1 diabetes]]; the odds ratio is 1.94, CI: 1.29-2.91, p = 0.0012, based on a study of Greek patients.

A study of RA patients from Crete also found that the [[rs7574865]](T) allele represented increased risk for [[rheumatoid arthritis]].{{PMID|18625278}}

{{PMID|18759272}} A study of 2,776 Spanish subjects found that the [[rs7574865]](T) allele was associated with [[rheumatoid arthritis]], [[Crohn's disease]], [[ulcerative colitis]], and [[type-1 diabetes]], but not with [[multiple sclerosis]].

{{PMID Auto
|PMID=19332627
|Title=Lack of Association Between STAT4 Gene Polymorphism and Biopsy-proven Giant Cell Arteritis
}}

{{PMID Auto GWAS
|PMID=18204098
|Trait=Systemic lupus erythematosus
|Title=Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX
|RiskAllele=T
|Pval=8.9999999999999995E-14
|OR=NR
|ORtxt=NR
}}
{{PMID Auto
|PMID=19479340
|Title=Association of STAT4 polymorphism with rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis
}}
{{PMID Auto
|PMID=19500629
|Title=STAT4 gene polymorphism is associated with psoriasis in the genetically homogeneous population of Crete, Greece
}}

{{PMID Auto
|PMID=19565500
|Title=Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis
|OA=1
}}
{{PMID Auto
|PMID=19404967
|Title=Confirmation of STAT4, IL2/IL21, and CTLA4 polymorphisms in rheumatoid arthritis
}}

{{omim
|desc=SYSTEMIC LUPUS ERYTHEMATOSUS, SUSCEPTIBILITY TO, 11; SLEB11
|id=612253
|rsnum=7574865
}}
{{PMID Auto
|PMID=19588142
|Title=Association between the rs7574865 polymorphism of STAT4 and rheumatoid arthritis: a meta-analysis
}}

{{omim
|desc=RHEUMATOID ARTHRITIS; RA
|id=180300
|rsnum=7574865
}}

{{omim
|desc=DIABETES MELLITUS, INSULIN-DEPENDENT, 7; IDDM7
|id=600321
|rsnum=7574865
}}

{{omim
|desc=SYSTEMIC LUPUS ERYTHEMATOSUS; SLE
|id=152700
|rsnum=7574865
}}

{{omim
|desc=INFLAMMATORY BOWEL DISEASE 1; IBD1
|id=266600
|rsnum=7574865
}}

{{omim
|id=600558
|desc=SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 4; STAT4
|rsnum=7574865
}}
{{PMID Auto
|PMID=19644887
|Title=STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis
}}
{{PMID Auto
|PMID=19714582
|Title=Rheumatoid arthritis does not share most of the newly identified systemic lupus erythematosus genetic factors
}}
{{PMID Auto
|PMID=19737838
|Title=A haplotype in STAT4 gene associated with rheumatoid arthritis in Caucasians is not associated in the Han Chinese population, but with the presence of rheumatoid factor
}}
{{PMID Auto
|PMID=19644876
|Title=Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome
}}

{{PMID Auto GWAS
|PMID=19838193
|Trait=Systemic lupus erythematosus
|Title=Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus
|RiskAllele=A
|Pval=5E-42
|OR=1.51
|ORtxt=[1.43-1.61]
}}
{{PMID Auto
|PMID=20039785
|Title=The Protein Tyrosine Phosphatase, Non-Receptor Type 22 R620W Polymorphism Does Not Confer Susceptibility to Psoriasis in the Genetic Homogeneous Population of Crete
}}
{{PMID Auto
|PMID=19877059
|Title=BANK1 is a genetic risk factor for diffuse cutaneous systemic sclerosis and has additive effects with IRF5 and STAT4
}}

{{PMID Auto
|PMID=19684152
|Title=Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population
}}

{{PMID Auto
|PMID=20176035
|Title=Association of signal transducer and activator of transcription 4 genetic variants with extra-intestinal manifestations in inflammatory bowel disease
}}

{{PMID Auto
|PMID=20438790
|Title=STAT4 polymorphism in a Chinese Han Population with Vogt-Koyanagi-Harada syndrome and Behcet's disease
}}
{{PMID Auto GWAS
|PMID=20453841
|Trait=Rheumatoid arthritis
|Title=A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility
|RiskAllele=T
|Pval=0.000002
|OR=1.17
|ORtxt=[1.10-1.25]
}}
{{PMID Auto GWAS
|PMID=20453842
|Trait=Rheumatoid arthritis
|Title=Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk lock
|RiskAllele=T
|Pval=3E-7
|OR=1.16
|ORtxt=[1.10-1.23]
}}
{{PMID Auto
|PMID=20498205
|Title=Investigation of potential non-HLA rheumatoid arthritis susceptibility loci in a European cohort increases the evidence for nine markers
|OA=1
}}
{{PMID Auto
|PMID=21163111
|Title=Variation in STAT4 is associated with systemic lupus erythematosus in Chinese Northern Han population
}}
{{PMID Auto
|PMID=21237270
|Title=Polymorphisms in STAT4 Increase the Risk of acute renal allograft rejection in the Chinese population
}}

{{omim
|id=181750
|rsnum=7574865
}}

{{PMID Auto
|PMID=21418779
|Title=Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders
}}

{{PMID Auto GWAS
|PMID=21383967
|Trait=None
|Title=Meta-Analysis of Genome-Wide Association Studies in Celiac Disease and Rheumatoid Arthritis Identifies Fourteen Non-HLA Shared Loci
|RiskAllele=T
|Pval=4E-10
|OR=None
|ORtxt=None
|OA=1
}}

{{PMID Auto GWAS
|PMID=21408207
|Trait=None
|Title=Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti-dsDNA Autoantibody Production
|RiskAllele=T
|Pval=0.000008
|OR=1.4100
|ORtxt=[1.21-1.63]
|OA=1
}}

{{PMID Auto
|PMID=21683716
|Title=Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population
}}

{{PMID Auto GWAS
|PMID=21750679
|Trait=None
|Title=Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.
|RiskAllele=T
|Pval=2E-13
|OR=1.3800
|ORtxt=[1.27-1.50]
|OA=1
}}

{{PMID Auto
|PMID=21968398
|Title=TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey
}}

{{PMID Auto
|PMID=22133489
|Title=The polymorphisms of T cell-specific TBX21 and STAT4 genes may contribute to the susceptibility of Chinese individuals to aplastic anemia
}}

{{PMID Auto
|PMID=22173230
|Title=A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis
}}

{{PMID Auto
|PMID=22483685
|Title=Interactions between IL17A, IL23R, and STAT4 polymorphisms confer susceptibility to intestinal Behcet's disease in Korean population
}}

{{PMID Auto
|PMID=22714917
|Title=Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis
}}

{{PMID Auto
|PMID=17932559
|Title=Association of STAT4 with rheumatoid arthritis in the Korean population.
|OA=1
}}

{{PMID Auto
|PMID=18432273
|Title=STAT4 but not TRAF1/C5 variants influence the risk of developing rheumatoid arthritis and systemic lupus erythematosus in Colombians.
}}

{{PMID Auto
|PMID=18434327
|Title=Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility.
|OA=1
}}

{{PMID Auto
|PMID=18579578
|Title=A risk haplotype of STAT4 for systemic lupus erythematosus is over-expressed, correlates with anti-dsDNA and shows additive effects with two risk alleles of IRF5.
|OA=1
}}

{{PMID Auto
|PMID=18794853
|Title=Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
|OA=1
}}

{{PMID Auto
|PMID=18803832
|Title=Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region.
|OA=1
}}

{{PMID Auto
|PMID=19019891
|Title=STAT4 associates with systemic lupus erythematosus through two independent effects that correlate with gene expression and act additively with IRF5 to increase risk.
|OA=1
}}

{{PMID Auto
|PMID=19109131
|Title=Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo.
|OA=1
}}

{{PMID Auto
|PMID=19116934
|Title=The chromosome 7q region association with rheumatoid arthritis in females in a British population is not replicated in a North American case-control series.
|OA=1
}}

{{PMID Auto
|PMID=19120275
|Title=STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes.
}}

{{PMID Auto
|PMID=19225526
|Title=Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese.
}}

{{PMID Auto
|PMID=19286670
|Title=The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.
}}

{{PMID Auto
|PMID=19287509
|Title=Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibody titer in adults with rheumatoid arthritis.
|OA=1
}}

{{PMID Auto
|PMID=19333953
|Title=High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups.
|OA=1
}}

{{PMID Auto
|PMID=19371230
|Title=STAT4 is not associated with type 2 diabetes in the genetically homogeneous population of Crete.
}}

{{PMID Auto
|PMID=19442287
|Title=Replication of recently identified systemic lupus erythematosus genetic associations: a case-control study.
|OA=1
}}

{{PMID Auto
|PMID=19445664
|Title=Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls.
|OA=1
}}

{{PMID Auto
|PMID=19458352
|Title=Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants.
|OA=1
}}

{{PMID Auto
|PMID=19591781
|Title=The search for lupus biomarkers.
|OA=1
}}

{{PMID Auto
|PMID=19605742
|Title=STAT4 single nucleotide polymorphism, rs7574865 G/T, as a risk for antiphospholipid syndrome.
}}

{{PMID Auto
|PMID=19674979
|Title=Overlap of disease susceptibility loci for rheumatoid arthritis and juvenile idiopathic arthritis.
|OA=1
}}

{{PMID Auto
|PMID=19838195
|Title=A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=19849816
|Title=Genetics of rheumatic disease.
|OA=1
}}

{{PMID Auto
|PMID=19923204
|Title=Genetic background of systemic sclerosis: autoimmune genes take centre stage.
}}

{{PMID Auto
|PMID=20018027
|Title=Conditional analysis of the major histocompatibility complex in rheumatoid arthritis.
|OA=1
}}

{{PMID Auto
|PMID=20018035
|Title=A combinatorial approach for detecting gene-gene interaction using multiple traits of Genetic Analysis Workshop 16 rheumatoid arthritis data.
|OA=1
}}

{{PMID Auto
|PMID=20018049
|Title=Evaluation of an optimal receiver operating characteristic procedure.
|OA=1
}}

{{PMID Auto
|PMID=20153791
|Title=STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: a replication study.
}}

{{PMID Auto
|PMID=20169177
|Title=Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=20353580
|Title=Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort.
|OA=1
}}

{{PMID Auto
|PMID=20360187
|Title=Influence of STAT4 polymorphism in primary Sjogren's syndrome.
}}

{{PMID Auto
|PMID=20439292
|Title=Genetic variants in the prediction of rheumatoid arthritis.
}}

{{PMID Auto
|PMID=20444755
|Title=Investigation of rheumatoid arthritis susceptibility genes identifies association of AFF3 and CD226 variants with response to anti-tumour necrosis factor treatment.
|OA=1
}}

{{PMID Auto
|PMID=20454450
|Title=Evidence for STAT4 as a common autoimmune gene: rs7574865 is associated with colonic Crohn's disease and early disease onset.
|OA=1
}}

{{PMID Auto
|PMID=20652065
|Title=Interferon alpha in systemic lupus erythematosus.
|OA=1
}}

{{PMID Auto
|PMID=20722033
|Title=The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1.
|OA=1
}}

{{PMID Auto
|PMID=21149496
|Title=NLRP1 influences the systemic sclerosis phenotype: a new clue for the contribution of innate immunity in systemic sclerosis-related fibrosing alveolitis pathogenesis.
}}

{{PMID Auto
|PMID=21167895
|Title=Association of genetic variations in the STAT4 and IRF7/KIAA1542 regions with systemic lupus erythematosus in a Northern Han Chinese population.
}}

{{PMID Auto
|PMID=21379322
|Title=Risk alleles for systemic lupus erythematosus in a large case-control collection and associations with clinical subphenotypes.
|OA=1
}}

{{PMID Auto
|PMID=21922340
|Title=Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset.
}}

{{PMID Auto
|PMID=22569826
|Title=Abnormal Genetic and Epigenetic Changes in Signal Transducer and Activator of Transcription 4 in the Pathogenesis of Inflammatory Bowel Diseases.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs7574865
|overall_frequency_n=93
|overall_frequency_d=122
|overall_frequency=0.762295
|n_genomes=48
|n_genomes_annotated=0
|n_haplomes=81
|n_articles=0
|n_articles_annotated=0
|in_gwas=Y
|autoscore=2
|webscore=N
}}

[[Scleroderma]]

{{PMID Auto GWAS
  |PMID=23053960
  |Trait=Systemic lupus erythematosus
  |Title=Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis.
  |RiskAllele=T
  |Pval=4E-14
  |OR=1.48
  |ORtxt=[1.335-1.634]
  }}

{{PMID Auto GWAS
  |PMID=23000144
  |Trait=Primary biliary cirrhosis
  |Title=Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population.
  |RiskAllele=T
  |Pval=1E-6
  |OR=1.35
  |ORtxt=[1.19-1.52]
  |OA=1
}}

{{PMID Auto GWAS
  |PMID=23273568
  |Trait=Systemic lupus erythematosus
  |Title=Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
  |RiskAllele=T
  |Pval=1E-21
  |OR=1.63
  |ORtxt=
  |OA=1
}}

{{PMID Auto GWAS
  |PMID=23242368
  |Trait=Hepatocellular carcinoma (hepatitis B virus related)
  |Title=Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.
  |RiskAllele=G
  |Pval=2E-10
  |OR=1.21
  |ORtxt=[1.14-1.28]
  }}

{{PMID Auto
|PMID=23727609
|Title=Replication study of STAT4 rs7574865 G/T polymorphism and risk of rheumatoid arthritis in a Chinese population
}}

{{PMID Auto
|PMID=23755762
|Title=STAT4 is a genetic risk factor for systemic sclerosis in a Chinese population
}}

{{PMID Auto
|PMID=23912645
|Title=Association of STAT4 rs7574865 with Susceptibility to Systemic Lupus Erythematosus in Iranian Population
}}

{{PMID Auto
|PMID=24023622
|Title=Analysis of Gender Differences in Genetic Risk: Association of TNFAIP3 Polymorphism with Male Childhood-Onset Systemic Lupus Erythematosus in the Japanese Population
|OA=1
}}

{{PMID Auto
|PMID=23360093
|Title=Association study of STAT4 polymorphisms and type 1 diabetes in Northeastern Chinese Han population
}}

{{PMID Auto
|PMID=24059108
|Title=[Signal transducer and activator of transcription 4 gene polymorphisms associated with dilated cardiomyopathy in Chinese Han population]
}}

{{PMID Auto
|PMID=22328738
|Title=Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.
|OA=1
}}

{{PMID Auto
|PMID=22402141
|Title=Positive association between STAT4 polymorphisms and polymyositis/dermatomyositis in a Japanese population.
}}

{{PMID Auto
|PMID=22753649
|Title=Variants within STAT genes reveal association with anticitrullinated protein antibody-negative rheumatoid arthritis in 2 European populations.
}}

{{PMID Auto
|PMID=22968431
|Title=Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs.
|OA=1
}}

{{PMID Auto
|PMID=23295549
|Title=Association between polymorphism in STAT4 gene and risk of rheumatoid arthritis: a meta-analysis.
}}

{{PMID Auto
|PMID=23450725
|Title=Susceptibility to childhood-onset rheumatoid arthritis: investigation of a weighted genetic risk score that integrates cumulative effects of variants at five genetic loci.
}}

{{PMID Auto
|PMID=23628400
|Title=Meta-analysis reveals an association of STAT4 polymorphisms with systemic autoimmune disorders and anti-dsDNA antibody.
}}

{{PMID Auto
|PMID=23777930
|Title=Investigation of juvenile idiopathic arthritis susceptibility loci: results from a Greek population.
}}

{{PMID Auto
|PMID=24204805
|Title=Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci in a Chinese population
}}

{{PMID Auto
|PMID=25097569
|Title=Association of STAT4 gene rs7574865G &gt; T polymorphism with ulcerative colitis risk: evidence from 1532 cases and 3786 controls
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}