What you carry at this position in your DNA and what research says about it.
Rheumatoid Arthritis Risk: 8/10 evidence, 11 publications.
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Sample genotype (not yours): G/G
Higher Risk of Rheumatoid Arthritis and Autoimmune Conditions
Two copies of the G allele are linked to an increased risk of developing rheumatoid arthritis and other chronic inflammatory diseases. This genotype is also associated with higher mortality rates if inflammatory joint conditions develop.
What this genotype means: Increased risk of developing rheumatoid arthritis; Higher likelihood of severe autoimmune inflammatory responses; Elevated risk of cardiovascular complications if joint disease is present.
Sample genotype (not yours): A/A
Typical Risk of Rheumatoid Arthritis
Two copies of the A allele represent the typical genetic baseline, carrying no elevated risk for rheumatoid arthritis or related autoimmune conditions. This genotype is associated with standard immune cell trafficking.
What this genotype means: Baseline risk for rheumatoid arthritis and autoimmune diseases; Typical long-term health outcomes if inflammatory conditions develop; No inherited elevation in endometriosis risk from this variant.
Sample genotype (not yours): G/A
Slightly Higher Risk of Rheumatoid Arthritis
One copy of the G allele is associated with a modest increase in the risk of rheumatoid arthritis and other autoimmune conditions. It represents an intermediate risk profile between the typical and high-risk genotypes.
What this genotype means: Modestly increased risk of rheumatoid arthritis; Slightly higher susceptibility to other inflammatory and autoimmune conditions; Intermediate risk of inflammatory disease complications.
Gene function and biological role
Gene Function: The CCL21 gene encodes a chemokine ligand that plays a critical role in directing the migration of immune cells, particularly T cells and dendritic cells [1]. It is highly expressed in lymphatic tissues and is essential for organizing immune responses [1]. By regulating lymphocyte trafficking, the gene helps coordinate how the body fights pathogens and maintains immune tolerance [1]. However, abnormal expression of this chemokine can lead to excessive immune cell recruitment to healthy tissues, driving chronic inflammation and autoimmune damage [2].
Variant Impact: Located within an intron of the CCL21 gene, rs2812378 is a single nucleotide polymorphism that influences immune system regulation. The G allele of this variant is associated with an increased susceptibility to rheumatoid arthritis and other chronic inflammatory conditions [1] [2]. Researchers believe this genetic change alters the trafficking of lymphocytes, leading to their accumulation in joints and other tissues [1]. In addition to susceptibility, this variant has been studied for its impact on disease severity and long-term health outcomes in patients with joint inflammation [3].
Key Insight: The G allele of this variant not only increases the risk of developing rheumatoid arthritis but is also associated with higher cardiovascular and all-cause mortality in patients who have inflammatory joint diseases.
Location: CCL21. Chromosome 9 · 9p13.3 · 34.7 Mb
Estimated prevalence by population
Global 11.7%; European 11.1%; African 16.9%; East Asian 0.5%; South Asian 11.5%; Americas 8.5%; Ashkenazi 7.4%; Finnish 6.8%; Middle Eastern 8.8%; Amish 10.2%.
Estimated GG genotype frequency.
Global 43.6%; European 44.4%; African 48.4%; East Asian 13.0%; South Asian 44.8%; Americas 41.4%; Ashkenazi 39.6%; Finnish 38.5%; Middle Eastern 41.7%; Amish 43.5%.
Estimated GA genotype frequency.
Global 44.7%; European 44.6%; African 34.6%; East Asian 86.5%; South Asian 43.8%; Americas 50.1%; Ashkenazi 53.1%; Finnish 54.7%; Middle Eastern 49.6%; Amish 46.3%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 18794853. ~1.2x Higher Risk.
Autoimmune Disease Risk. Evidence: 6/10. Source: PMID 26974007. Increased Risk.
Inflammatory & Circulating Protein Markers
Inflammation-Related Mortality. Evidence: 3/10. Source: PMID 20461788. ~1.4x Higher Risk.
Endocrine & Reproductive
Female Reproductive Health & Fertility
Endometriosis. Evidence: 3/10. Source: PMID 20797713. Increased Risk.
Showing effects for A/A genotype
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 18794853. Typical Risk.
Autoimmune Disease Risk. Evidence: 6/10. Source: PMID 26974007. Typical Risk.
Inflammation-Related Mortality. Evidence: 3/10. Source: PMID 20461788. Typical Risk.
Endometriosis. Evidence: 3/10. Source: PMID 20797713. Typical Risk.
Showing effects for G/A genotype
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 18794853. ~1.1x Higher Risk.
Autoimmune Disease Risk. Evidence: 6/10. Source: PMID 26974007. Slightly Increased.
Inflammation-Related Mortality. Evidence: 3/10. Source: PMID 20461788. Slightly Higher Risk.
Endometriosis. Evidence: 3/10. Source: PMID 20797713. Slightly Increased.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele significantly increases susceptibility to rheumatoid arthritis [1]. This genetic profile is associated with elevated levels of anti-CCP antibodies and rheumatoid factor, which are key markers of autoimmune joint destruction [2]. Beyond arthritis, this genotype is linked to a broader vulnerability to chronic inflammatory diseases, including celiac disease, psoriasis, and Crohn's disease [3]. Clinical studies have also shown that individuals with this genotype who develop inflammatory polyarthritis face a 40% higher risk of all-cause mortality, often driven by cardiovascular complications [4]. Furthermore, research indicates a potential association with moderate to severe endometriosis, highlighting the widespread impact of altered immune cell trafficking [5].
Increased risk of developing rheumatoid arthritis; Higher likelihood of severe autoimmune inflammatory responses; Elevated risk of cardiovascular complications if joint disease is present.
Sample genotype: AA (Homozygous)
Carrying two copies of the protective A allele means there is no inherited elevation in the risk of rheumatoid arthritis from this variant [1]. This genotype is associated with typical levels of autoantibodies and standard joint health [2]. Individuals with this genetic profile do not carry the increased risk for other chronic inflammatory diseases, such as Crohn's disease, celiac disease, or psoriasis, that is seen with the G allele [3]. Furthermore, if inflammatory joint conditions do develop, this genotype is associated with a lower risk of premature mortality and cardiovascular complications compared to risk-allele carriers [4]. There is also no elevated risk for moderate to severe endometriosis linked to this locus [5].
Baseline risk for rheumatoid arthritis and autoimmune diseases; Typical long-term health outcomes if inflammatory conditions develop; No inherited elevation in endometriosis risk from this variant.
Sample genotype: GA (Heterozygous)
Carrying one copy of the G allele confers a moderate increase in susceptibility to rheumatoid arthritis compared to the typical genotype [1]. This intermediate profile is associated with a slightly higher likelihood of producing autoantibodies like rheumatoid factor, which contribute to joint inflammation [2]. The presence of the G allele also elevates the risk of other chronic inflammatory conditions, such as psoriasis and celiac disease, due to altered lymphocyte homing [3]. In patients with existing inflammatory polyarthritis, carrying a single risk allele is associated with a moderately increased risk of cardiovascular and all-cause mortality [4]. Additionally, this genotype has been linked to a slightly higher risk of developing moderate to severe endometriosis [5].
Modestly increased risk of rheumatoid arthritis; Slightly higher susceptibility to other inflammatory and autoimmune conditions; Intermediate risk of inflammatory disease complications.
Variants with shared genetic architecture
rs4750316 · LINC02656 Gene · Chr 10 · Rheumatoid Arthritis Risk
rs6910071 · TSBP1 Gene · Chr 6 · Rheumatoid Arthritis Risk
rs660895 · HLA-DRB1 Gene · Chr 6 · Rheumatoid Arthritis Risk
Common variants at CD40 and other loci confer risk of rheumatoid arthritis.
Content updated August 2026.
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