What you carry at this position in your DNA and what research says about it.
Autoimmune Disease Risk: 6/10 evidence, 17 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): A/A
Higher Risk of Autoimmune Conditions
Carrying two copies of the A allele is associated with an increased risk of developing multiple sclerosis, psoriasis, and other autoimmune diseases. However, individuals with this genotype who develop psoriasis may respond better to certain anti-TNF biologic treatments.
What this genotype means: Increased risk of multiple sclerosis; Increased risk of psoriasis; Better response to certain anti-TNF therapies.
Sample genotype (not yours): A/G
Moderately Increased Autoimmune Risk
Carrying one copy of the A allele is associated with a moderately increased risk of multiple sclerosis, psoriasis, and other autoimmune conditions. It may also influence response rates to anti-TNF biologic medications.
What this genotype means: Moderately increased risk of multiple sclerosis; Moderately increased risk of psoriasis; Variable response to anti-TNF therapies.
Sample genotype (not yours): G/G
Lower Risk of Autoimmune Conditions
Carrying two copies of the G allele is associated with a lower risk of developing multiple sclerosis, psoriasis, and other autoimmune diseases. However, it may be linked to a poorer response to certain anti-TNF biologic treatments if psoriasis does develop.
What this genotype means: Lower risk of multiple sclerosis; Lower risk of psoriasis; Poorer response to certain anti-TNF therapies.
Gene function and biological role
Gene Function: The IL12B gene encodes the p40 subunit shared by two critical immune system cytokines, interleukin-12 (IL-12) and interleukin-23 (IL-23). These signaling proteins play a central role in directing the growth and activation of T-cells, which are key players in the body's defense system. When these cytokines are overactive, they can mistakenly drive inflammatory pathways that attack the body's own tissues. Consequently, genetic variations in this gene are heavily implicated in several autoimmune conditions [1]. Understanding how this gene behaves helps researchers design targeted therapies that block these specific inflammatory pathways [2].
Variant Impact: The rs2546890 variant is a regulatory genetic change located near the IL12B gene that influences how the gene is expressed. By altering the regulatory activity, this variant can shift the balance of inflammatory cytokines like interleukin-23 in the body [3]. The A allele is associated with an increased susceptibility to multiple autoimmune disorders, including multiple sclerosis and psoriasis [1]. Conversely, the G allele is linked to lower risks of these conditions but may influence how patients respond to certain anti-inflammatory medications [4].
Key Insight: This variant acts as a shared genetic link across multiple distinct autoimmune diseases, demonstrating how a single immune pathway can trigger different conditions in different people.
Location: IL12B. Chromosome 5 · 5q33.3 · 159.3 Mb
Estimated prevalence by population
Global 23.3%; European 27.2%; African 15.2%; East Asian 18.8%; South Asian 32.3%; Americas 17.7%; Ashkenazi 22.5%; Finnish 35.4%; Middle Eastern 18.4%; Amish 35.6%.
Estimated AA genotype frequency.
Global 49.0%; European 49.9%; African 47.6%; East Asian 49.1%; South Asian 49.1%; Americas 48.8%; Ashkenazi 49.9%; Finnish 48.2%; Middle Eastern 49.0%; Amish 48.1%.
Estimated AG genotype frequency.
Global 27.8%; European 22.9%; African 37.3%; East Asian 32.1%; South Asian 18.6%; Americas 33.5%; Ashkenazi 27.6%; Finnish 16.4%; Middle Eastern 32.6%; Amish 16.3%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Immunity & Inflammation
Autoimmune Diseases
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. ~1.1x Risk.
Lupus. Evidence: 6/10. Source: PMID 36750564. Increased Risk.
Organ Systems
Skin & Hair Conditions
Psoriasis. Evidence: 6/10. Source: PMID 20953188. ~1.5x Risk.
Liver Function & Disease
Autoimmune Liver Disease. Evidence: 6/10. Source: PMID 26394269. ~1.15x Risk.
Pharmacogenomics
Immunosuppressant & Biologic Response
Anti-TNF Drug Response. Evidence: 5/10. Source: PMID 27670765. Stronger Response.
Showing effects for A/G genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. Increased Risk.
Psoriasis. Evidence: 6/10. Source: PMID 20953188. Increased Risk.
Autoimmune Liver Disease. Evidence: 6/10. Source: PMID 26394269. Increased Risk.
Anti-TNF Drug Response. Evidence: 5/10. Source: PMID 27670765. Mixed Response.
Showing effects for G/G genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 21833088. Typical Risk.
Lupus. Evidence: 6/10. Source: PMID 36750564. Typical Risk.
Psoriasis. Evidence: 6/10. Source: PMID 20953188. Typical Risk.
Autoimmune Liver Disease. Evidence: 6/10. Source: PMID 26394269. Typical Risk.
Anti-TNF Drug Response. Evidence: 5/10. Source: PMID 27670765. Poorer Response.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Having two copies of the A allele significantly elevates the risk of several autoimmune disorders. Large-scale genetic studies have linked this genotype to a higher susceptibility to multiple sclerosis [1]. It is also associated with an increased risk of psoriasis, a chronic inflammatory skin condition [2]. Furthermore, research connects this genetic profile to a higher likelihood of developing primary biliary cholangitis, which affects the liver [3]. Systemic lupus erythematosus is another autoimmune condition with elevated risk for carriers of this genotype [4]. On the therapeutic side, individuals with this genotype who require treatment for moderate-to-severe plaque psoriasis tend to have a more favorable response to anti-TNF biologic therapies like adalimumab and infliximab [5]. This highlights how genetic variants can simultaneously increase disease risk while predicting better treatment outcomes. These findings suggest that while the baseline risk for inflammation is higher, therapeutic options may be highly effective if needed.
Increased risk of multiple sclerosis; Increased risk of psoriasis; Better response to certain anti-TNF therapies.
Sample genotype: AG (Heterozygous)
Having one copy of the A allele and one copy of the G allele places individuals at an intermediate risk level for several autoimmune conditions. This genotype is linked to an elevated risk of multiple sclerosis compared to those with the protective G/G genotype [1]. It also increases susceptibility to psoriasis, causing a moderate rise in baseline risk [2]. Additionally, research indicates a higher likelihood of developing primary biliary cholangitis, an autoimmune liver disease [3]. In terms of medical treatment, individuals with this genotype show mixed responses to anti-TNF biologic therapies. Some studies indicate a poorer response to etanercept when treating moderate-to-severe plaque psoriasis [4]. Conversely, other research shows a reasonable response to adalimumab and infliximab [5]. This genetic profile underscores the complex balance between disease susceptibility and medication efficacy.
Moderately increased risk of multiple sclerosis; Moderately increased risk of psoriasis; Variable response to anti-TNF therapies.
Sample genotype: GG (Homozygous)
Having two copies of the G allele provides a protective effect against several autoimmune disorders. This genotype is associated with a significantly lower risk of developing multiple sclerosis [1]. It also correlates with a reduced susceptibility to psoriasis, keeping baseline inflammatory risks lower [2]. Furthermore, research connects this genetic profile to a lower likelihood of developing primary biliary cholangitis [3]. Systemic lupus erythematosus is another autoimmune condition where this genotype offers a protective advantage [4]. While this genetic profile is highly favorable for avoiding these inflammatory conditions, it has a caveat regarding treatment. If an autoimmune condition like psoriasis does develop, individuals with this genotype may have a poorer response to anti-TNF biologic therapies such as etanercept [5]. Nevertheless, the overall health outlook remains positive due to the reduced baseline risk of these chronic diseases.
Lower risk of multiple sclerosis; Lower risk of psoriasis; Poorer response to certain anti-TNF therapies.
Variants with shared genetic architecture
rs12188300 · IL12B Gene · Chr 5 · Psoriasis Risk
rs3213094 · IL12B Gene · Chr 5 · Psoriasis and Biologic Response
rs10045431 · IL12B Gene · Chr 5 · Inflammatory Bowel Disease Risk
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
Polymorphisms associated with etanercept response in moderate-to-severe plaque psoriasis.
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