What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 8/10 evidence, 74 publications.
You're viewing every possible genotype for this variant.
None of these is your result. Use the genotype toggle to compare them, then sign up and upload your DNA to see which one is yours.
Sample genotype (not yours): T/T
Significantly Higher Autoimmune Disease Risk
Elevated susceptibility to several autoimmune conditions, including lupus and rheumatoid arthritis, is a primary feature of this genetic profile. Immune cells tend to produce higher levels of inflammatory signals, which can also affect responses to biologic therapies and statins. Conversely, this profile is associated with a lower risk of developing hepatitis B-related liver cancer.
What this genotype means: Up to 2.4x higher risk of systemic lupus erythematosus; Up to 1.69x higher risk of rheumatoid arthritis; Increased risk of Sjögren's syndrome and systemic sclerosis.
Sample genotype (not yours): G/G
Typical Autoimmune Risk, Slightly Higher Liver Cancer Risk
Baseline susceptibility to autoimmune diseases like lupus and rheumatoid arthritis is typical for this genetic profile. Although it avoids the elevated inflammatory risks seen with other profiles, it is linked to a slightly higher risk of liver cancer, particularly in those with chronic hepatitis B. Standard responses to common biologic therapies and statins are also expected.
What this genotype means: Typical baseline risk for lupus and rheumatoid arthritis; Typical baseline risk for Sjögren's syndrome; Standard response to TNF inhibitor therapies.
Sample genotype (not yours): T/G
Moderately Higher Autoimmune Disease Risk
Moderate susceptibility to autoimmune disorders such as lupus, rheumatoid arthritis, and Sjögren's syndrome characterizes this genetic profile. Increased inflammatory activity in immune cells may also influence how the body processes certain biologic treatments and statins. On the other hand, this profile offers some protection against hepatitis B-related liver cancer.
What this genotype means: About 1.55x higher risk of systemic lupus erythematosus; About 1.3x higher risk of rheumatoid arthritis; Moderately increased risk of Sjögren's syndrome.
Gene function and biological role
Gene Function: STAT4 encodes a critical transcription factor that regulates key aspects of the human immune response [1]. It is activated by chemical messengers like interleukin-12 and type I interferons, which are vital for defending the body against pathogens. Once activated, STAT4 drives the development of specialized inflammatory T cells, specifically Th1 and Th17 helper cells [2]. These cells produce powerful cytokines such as interferon-gamma to coordinate immune defenses [3]. However, when STAT4 signaling is overly active, it can cause the immune system to mistakenly attack the body's own tissues, leading to chronic inflammation and autoimmune diseases [4].
Variant Impact: The rs7574865 variant is located in an intron of the STAT4 gene and serves as a major genetic regulator of its activity [4]. Carrying the T allele increases the expression of STAT4 messenger RNA and protein in immune cells [3]. This genetic change makes immune cells hyper-sensitive to interferon-alpha, leading to elevated inflammatory gene expression [5]. While this heightened state of alert helps the immune system clear certain viral infections, it significantly increases the risk of developing autoimmune conditions. Conversely, the G allele is associated with lower STAT4 expression, which protects against autoimmunity but may slightly reduce the efficiency of viral clearance in the liver [6].
Key Insight: This variant represents a classic evolutionary trade-off where the exact same genetic allele that increases susceptibility to autoimmune diseases like lupus actually helps protect the body against hepatitis B-related liver cancer.
Location: STAT4. Chromosome 2 · 2q32.2 · 191.1 Mb
Estimated prevalence by population
Global 4.9%; European 4.9%; African 1.9%; East Asian 12.4%; South Asian 8.2%; Americas 9.3%; Ashkenazi 5.4%; Finnish 5.3%; Middle Eastern 7.0%; Amish 3.6%.
Estimated TT genotype frequency.
Global 33.1%; European 34.5%; African 24.0%; East Asian 45.7%; South Asian 40.9%; Americas 42.4%; Ashkenazi 35.6%; Finnish 35.4%; Middle Eastern 38.8%; Amish 30.9%.
Estimated TG genotype frequency.
Global 62.0%; European 60.6%; African 74.1%; East Asian 41.9%; South Asian 50.9%; Americas 48.2%; Ashkenazi 59.0%; Finnish 59.3%; Middle Eastern 54.2%; Amish 65.5%.
Estimated GG genotype frequency.
Showing effects for T/T genotype
Immunity & Inflammation
Autoimmune Diseases
Lupus. Evidence: 8/10. Source: PMID 18204098. ~2.4x Risk.
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 20453841. ~1.69x Risk.
Sjogren's Syndrome. Evidence: 4/10. Source: PMID 28076899. ~2.28x Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 21750679. ~1.4x Risk.
Cancer & Oncology
Gastrointestinal Cancers
Liver Cancer. Evidence: 6/10. Source: PMID 23242368. Lower Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Etanercept Response. Evidence: 5/10. Source: PMID 28107378. Poorer Response.
Lipid-Lowering Drug Response
Statin Liver Safety. Evidence: 5/10. Source: PMID 22968431. Higher Injury Risk.
Showing effects for G/G genotype
Lupus. Evidence: 8/10. Source: PMID 18204098. Typical Risk.
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 20453841. Typical Risk.
Sjogren's Syndrome. Evidence: 4/10. Source: PMID 28076899. Typical Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 21750679. Typical Risk.
Liver Cancer. Evidence: 6/10. Source: PMID 23242368. ~1.21x Risk.
Etanercept Response. Evidence: 5/10. Source: PMID 28107378. Typical Response.
Statin Liver Safety. Evidence: 5/10. Source: PMID 22968431. Typical Risk.
Showing effects for T/G genotype
Lupus. Evidence: 8/10. Source: PMID 18204098. ~1.55x Risk.
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 20453841. ~1.3x Risk.
Sjogren's Syndrome. Evidence: 4/10. Source: PMID 28076899. ~1.42x Risk.
Systemic Sclerosis. Evidence: 6/10. Source: PMID 21750679. Slightly Increased.
Liver Cancer. Evidence: 6/10. Source: PMID 23242368. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele significantly increases the risk of developing several autoimmune conditions. Research shows a 2.4-fold increase in the risk of systemic lupus erythematosus and a 1.69-fold increase in rheumatoid arthritis risk [1]. This genetic profile is also associated with a more than doubled risk of Sjögren's syndrome and an elevated risk of systemic sclerosis [2]. The underlying mechanism involves increased STAT4 expression, which hyper-sensitizes immune cells to inflammatory signals like interferon-alpha [3]. This hyper-reactivity can also lead to a poorer response to tumor necrosis factor inhibitors like etanercept [4]. Additionally, there is an increased likelihood of experiencing liver injury when taking statin medications [5]. However, the heightened immune activity associated with this profile appears to offer protection against hepatitis B-related liver cancer [6].
Up to 2.4x higher risk of systemic lupus erythematosus; Up to 1.69x higher risk of rheumatoid arthritis; Increased risk of Sjögren's syndrome and systemic sclerosis; Potential for reduced effectiveness of certain biologic therapies; Slightly lower risk of hepatitis B-related liver cancer.
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele is associated with a typical, baseline risk for most autoimmune diseases. This profile avoids the elevated risks of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome seen in T allele carriers [1]. Immune cells in individuals with this genotype express typical levels of STAT4, leading to standard inflammatory responses [2]. Consequently, standard responses to TNF inhibitors like etanercept and typical tolerance to statin medications are expected [3] [4]. However, the lower baseline immune activation associated with this profile may reduce the body's ability to clear certain viral infections. Specifically, the G/G genotype is linked to a slightly increased risk of chronic hepatitis B infection and subsequent liver cancer [5]. This trade-off highlights how genetic variants that protect against one class of disease can sometimes increase susceptibility to another [6].
Typical baseline risk for lupus and rheumatoid arthritis; Typical baseline risk for Sjögren's syndrome; Standard response to TNF inhibitor therapies; Slightly increased risk of hepatitis B-related liver cancer; Typical tolerance to statin medications.
Sample genotype: TG (Heterozygous)
Carrying one copy of the T allele is associated with a moderate increase in the risk of various autoimmune disorders. Studies indicate a 1.55-fold increase in the risk of systemic lupus erythematosus and a 1.3-fold increase in rheumatoid arthritis risk [1]. There is also a moderately elevated risk for Sjögren's syndrome, systemic sclerosis, and primary biliary cholangitis [2]. This intermediate risk stems from a moderate increase in STAT4 expression, which slightly elevates immune cell sensitivity to interferon-alpha [3]. This altered immune state can lead to a poorer response to TNF inhibitors like etanercept [4]. It is also linked to a higher risk of liver sensitivity when using statin medications [5]. On the positive side, having one T allele provides a protective effect against the development of hepatitis B-related liver cancer compared to the G/G genotype [6].
About 1.55x higher risk of systemic lupus erythematosus; About 1.3x higher risk of rheumatoid arthritis; Moderately increased risk of Sjögren's syndrome; Slightly higher likelihood of statin-related liver sensitivity; Moderate protection against hepatitis B-related liver cancer.
Variants with shared genetic architecture
rs11889341 · STAT4 Gene · Chr 2 · Autoimmune Disease Risk
rs3821236 · STAT4 Gene · Chr 2 · Autoimmune Disease Risk
rs7582694 · STAT4 Gene · Chr 2 · Autoimmune Disease Risk
Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis.
Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.
Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs.
Content updated August 2026.
ReadYourDNA provides educational interpretation of DNA data you already have. It is not diagnostic, not a substitute for professional medical advice, diagnosis, or treatment, and is not intended to diagnose, treat, cure, or prevent any disease. Talk to a clinician before acting on any result.
Raw DNA Data Reports for 23andMe & AncestryDNA · About ReadYourDNA · FAQ · Methodology & Science · Pricing · Support and complaints · Legal & Contact · Health Traits · Pharmacogenomics · Carrier Status · Variant Explorer · The Human Karyotype · Privacy Policy · Terms of Service · Accessibility · Consumer Health Data Privacy · Your Privacy Choices · Editorial Standards · Your Data, Checkable · Sample Report · ReadYourDNA and Promethease compared · What is inside a 23andMe raw data file · What is inside an AncestryDNA raw data file · What a chatbot can and cannot do with your raw DNA file · Where a raw DNA file can still be uploaded in 2026
Written, maintained and operated by Martin Pechhacker, sole proprietor, Vienna, Austria. Trade register GISA 40064420. support@readyourdna.com