What you carry at this position in your DNA and what research says about it.
Rheumatoid Arthritis Risk: 6/10 evidence, 39 publications.
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Sample genotype (not yours): T/T
Lower Risk of Rheumatoid Arthritis
Carrying two copies of the protective T allele is associated with a reduced risk of developing rheumatoid arthritis and systemic lupus erythematosus. This genetic profile is linked to lower levels of key inflammatory proteins.
What this genotype means: Reduced risk of rheumatoid arthritis; Lower systemic inflammation markers; Decreased risk of systemic lupus erythematosus.
Sample genotype (not yours): G/G
Typical Risk of Rheumatoid Arthritis
Carrying two copies of the common G allele represents the standard genetic baseline for rheumatoid arthritis and lupus risk. This profile is associated with typical levels of immune cell activation.
What this genotype means: Typical baseline risk for rheumatoid arthritis; Standard CD40 receptor expression; Typical levels of inflammatory markers.
Sample genotype (not yours): T/G
Carrying one copy of the protective T allele is associated with a reduced risk of developing rheumatoid arthritis and systemic lupus erythematosus. This genetic profile helps keep inflammatory signaling in check.
What this genotype means: Reduced risk of rheumatoid arthritis; Moderated inflammatory signaling; Decreased risk of systemic lupus erythematosus.
Gene function and biological role
Gene Function: The CD40 gene encodes a critical receptor protein found on the surface of various immune cells, including B cells and dendritic cells [1]. This receptor plays a central role in activating the immune system by binding to its partner ligand on T cells [2]. When activated, CD40 signaling drives the proliferation of antibody-producing cells and coordinates inflammatory responses [1]. Because of its powerful role in immune activation, variations in this gene are heavily linked to autoimmune diseases [3]. Proper regulation of this pathway is essential to prevent the immune system from mistakenly attacking the body's own tissues [1].
Variant Impact: The rs4810485 variant is an intron variant located within the CD40 gene that influences how much CD40 protein is produced [4]. A change from the common G allele to the minor T allele is associated with altered CD40 expression levels on immune cells [5]. This alteration in protein levels directly impacts the strength of downstream inflammatory signaling pathways [4]. Consequently, this single genetic change has been shown to modify susceptibility to several chronic inflammatory conditions, particularly rheumatoid arthritis and systemic lupus erythematosus [3]. The protective effect of the minor allele has been replicated across multiple large-scale genetic studies [1].
Key Insight: A single letter change in this gene lowers the risk of rheumatoid arthritis by over ten percent, but the very same allele raises the risk of multiple sclerosis. It also influences levels of tumor necrosis factor, a key inflammatory protein targeted by major autoimmune medications.
Location: CD40. Chromosome 20 · 20q13.12 · 46.1 Mb
Estimated prevalence by population
Global 5.4%; European 6.6%; African 0.7%; East Asian 19.1%; South Asian 7.0%; Americas 5.2%; Ashkenazi 7.4%; Finnish 7.7%; Middle Eastern 7.6%; Amish 5.8%.
Estimated TT genotype frequency.
Global 32.1%; European 38.2%; African 15.1%; East Asian 49.2%; South Asian 39.0%; Americas 35.3%; Ashkenazi 39.7%; Finnish 40.0%; Middle Eastern 39.9%; Amish 36.6%.
Estimated TG genotype frequency.
Global 62.5%; European 55.1%; African 84.2%; East Asian 31.7%; South Asian 54.0%; Americas 59.5%; Ashkenazi 52.9%; Finnish 52.3%; Middle Eastern 52.5%; Amish 57.6%.
Estimated GG genotype frequency.
Showing effects for T/T genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 18794853. ~13% Lower Risk.
Lupus. Evidence: 5/10. Source: PMID 28714469. Lower Risk.
Multiple Sclerosis. Evidence: 6/10. Source: PMID 24076602. ~1.2x Higher Risk.
Inflammatory & Circulating Protein Markers
TNF Levels. Evidence: 8/10. Source: PMID 33067605. Lower Levels.
Cardiovascular & Metabolic
Blood Cell & Iron Traits
Lymphocyte Count. Evidence: 6/10. Source: PMID 32929287. Lower Count.
Showing effects for G/G genotype
Rheumatoid Arthritis. Evidence: 6/10. Source: PMID 18794853. Typical Risk.
Lupus. Evidence: 5/10. Source: PMID 28714469. Typical Risk.
Multiple Sclerosis. Evidence: 6/10. Source: PMID 24076602. Typical Risk.
TNF Levels. Evidence: 8/10. Source: PMID 33067605. Typical Levels.
Lymphocyte Count. Evidence: 6/10. Source: PMID 32929287. Typical Count.
Showing effects for T/G genotype
Multiple Sclerosis. Evidence: 6/10. Source: PMID 24076602. Slightly Higher Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Inheriting two copies of the minor T allele provides a protective advantage against rheumatoid arthritis and lupus specifically, rather than against autoimmune disease in general. Large-scale genetic analyses demonstrate that this genotype is associated with an approximately thirteen percent reduction in the risk of developing rheumatoid arthritis [1]. This protective effect is driven by a reduction in CD40 protein expression, which tempers the activity of immune cells [2]. Lower CD40 signaling leads to decreased levels of tumor necrosis factor, a major driver of systemic inflammation [3]. Additionally, this genotype is linked to a lower risk of systemic lupus erythematosus, another chronic autoimmune condition [4]. The same T allele runs the opposite way for multiple sclerosis, where it is the risk allele rather than the protective one, carrying roughly a twenty percent higher risk with two copies [6]. This trade-off is well documented at this gene. The protective effect against rheumatoid arthritis is clearest in populations of European ancestry and may vary in other ancestral groups [5].
Reduced risk of rheumatoid arthritis; Lower systemic inflammation markers; Decreased risk of systemic lupus erythematosus; Slightly higher risk of multiple sclerosis.
Sample genotype: GG (Homozygous)
Inheriting two copies of the common G allele represents the standard genetic baseline found in the majority of the global population. This genotype does not carry the protective benefits of the minor T allele, meaning there is a typical risk for developing rheumatoid arthritis [1]. Without the moderating influence of the T allele, CD40 receptor expression remains at standard levels, allowing for typical immune cell activation and signaling [2]. This standard signaling pathway is associated with typical levels of tumor necrosis factor and other inflammatory cytokines [3]. Consequently, there is no genetic reduction in the risk for systemic lupus erythematosus or other related autoimmune conditions [4]. Understanding this baseline risk is helpful for overall health tracking, though lifestyle and environmental factors play a much larger role in actual disease development [5].
Typical baseline risk for rheumatoid arthritis; Standard CD40 receptor expression; Typical levels of inflammatory markers.
Sample genotype: TG (Heterozygous)
Inheriting one copy of the protective T allele and one copy of the common G allele lowers the risk of rheumatoid arthritis and lupus specifically, rather than of autoimmune disease in general. Clinical studies show that this heterozygous profile is linked to a thirteen percent lower risk of rheumatoid arthritis compared to the typical baseline [1]. The presence of the T allele helps moderate the expression of the CD40 receptor on immune cells [2]. This reduction in receptor density leads to calmer immune responses and lower levels of circulating inflammatory markers like tumor necrosis factor [3]. Furthermore, this genotype is associated with a decreased susceptibility to systemic lupus erythematosus [4]. The same T allele carries a slightly higher risk of multiple sclerosis, which runs opposite to its protective effect in rheumatoid arthritis [6]. The rheumatoid-arthritis benefit is well documented in European populations and less pronounced in East Asian cohorts [5].
Reduced risk of rheumatoid arthritis; Moderated inflammatory signaling; Decreased risk of systemic lupus erythematosus; Slightly higher risk of multiple sclerosis.
Variants with shared genetic architecture
rs1883832 · CD40 Gene · Chr 20 · Autoimmune Disease Risk
rs1569723 · CD40 Gene · Chr 20 · Inflammatory Disease Risk
rs6074022 · CD40 Gene · Chr 20 · Autoimmune Disease Risk
Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study.
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations.
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
Content updated August 2026.
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