What you carry at this position in your DNA and what research says about it.
Rheumatoid Arthritis Risk: 8/10 evidence, 35 publications.
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Sample genotype (not yours): A/A
Typical Autoimmune Risk
This genotype is associated with baseline risk for rheumatoid arthritis and other related autoimmune conditions. It represents the most common genetic profile globally.
What this genotype means: Typical risk of rheumatoid arthritis; Typical risk of IgA nephropathy.
Sample genotype (not yours): A/G
Slightly Elevated Autoimmune Risk
Carrying one copy of the G allele is linked to a moderately increased risk of rheumatoid arthritis and IgA nephropathy. It also provides a protective effect against Parkinson's disease.
What this genotype means: Moderately higher risk of rheumatoid arthritis; Slightly higher risk of IgA nephropathy; Reduced risk of Parkinson's disease.
Sample genotype (not yours): G/G
Significantly Higher Rheumatoid Arthritis Risk
Carrying two copies of the G allele is associated with a roughly 6-fold higher risk of rheumatoid arthritis. It also correlates with a reduced risk of Parkinson's disease.
What this genotype means: Significantly higher risk of rheumatoid arthritis; Increased risk of IgA nephropathy; Significantly lower risk of Parkinson's disease.
Gene function and biological role
Gene Function: The HLA-DRB1 gene belongs to a family of genes called the human leukocyte antigen complex, which helps the immune system distinguish the body's own proteins from foreign invaders [1]. This gene specifically provides instructions for making a protein that plays a critical role in presenting foreign antigens to immune cells [1]. Variations in this gene are highly polymorphic and are strongly linked to various autoimmune conditions [2]. When the immune system misidentifies healthy tissue as a threat, it can trigger chronic inflammation and tissue damage [2].
Variant Impact: The rs660895 variant is an intergenic marker that serves as a reliable tag for the HLA-DRB1*0401 immune system allele [1]. Carrying the G allele at this position correlates with the presence of this specific immune variant, which alters how immune cells recognize joint tissues [1]. This genetic marker is one of the most heavily studied risk factors for autoimmune joint disease [2]. It is also associated with changes in other inflammatory markers and susceptibility to specific kidney conditions [3].
Key Insight: The G allele significantly increases the risk of rheumatoid arthritis, but interestingly, research shows it may offer a protective effect against developing Parkinson's disease.
Location: HLA-DRB1. Chromosome 6 · 6p21.32 · 32.6 Mb
Estimated prevalence by population
Global 64.9%; European 65.0%; African 73.0%; East Asian 53.7%; South Asian 76.1%; Americas 50.2%; Ashkenazi 62.2%; Finnish 55.6%; Middle Eastern 69.4%; Amish 63.4%.
Estimated AA genotype frequency.
Global 31.0%; European 31.2%; African 24.9%; East Asian 39.2%; South Asian 22.3%; Americas 41.3%; Ashkenazi 33.3%; Finnish 37.9%; Middle Eastern 27.8%; Amish 32.5%.
Estimated AG genotype frequency.
Global 4.0%; European 3.8%; African 2.1%; East Asian 7.2%; South Asian 1.6%; Americas 8.5%; Ashkenazi 4.5%; Finnish 6.5%; Middle Eastern 2.8%; Amish 4.2%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Immunity & Inflammation
Autoimmune Diseases
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 29168332. Typical Risk.
Inflammatory & Circulating Protein Markers
Interleukin-6 Levels. Evidence: 5/10. Source: PMID 33517400. Typical Levels.
Organ Systems
Kidney Function & Disease
IgA Nephropathy. Evidence: 7/10. Source: PMID 22197929. Typical Risk.
Neurology & Mental Health
Neurodegenerative Diseases
Parkinson's Disease. Evidence: 3/10. Source: PMID 22807207. Typical Risk.
Showing effects for A/G genotype
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 29168332. Slightly Increased.
Interleukin-6 Levels. Evidence: 5/10. Source: PMID 33517400. Slightly Higher.
IgA Nephropathy. Evidence: 7/10. Source: PMID 22197929. Increased Risk.
Parkinson's Disease. Evidence: 3/10. Source: PMID 22807207. Lower Risk.
Showing effects for G/G genotype
Rheumatoid Arthritis. Evidence: 8/10. Source: PMID 29168332. ~6x Higher Risk.
Interleukin-6 Levels. Evidence: 5/10. Source: PMID 33517400. Higher Levels.
IgA Nephropathy. Evidence: 7/10. Source: PMID 22197929. Higher Risk.
Parkinson's Disease. Evidence: 3/10. Source: PMID 22807207. Lowest Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Having two copies of the A allele means you do not carry the HLA-DRB1*0401 risk variant tagged by this SNP [1]. Consequently, your genetic risk for developing rheumatoid arthritis remains at the typical baseline level [1]. This genotype is also associated with typical baseline risks for IgA nephropathy, a type of kidney disease [2]. However, because you lack the G allele, you do not inherit the potential protective effect against Parkinson's disease observed in G carriers [3]. Overall, this profile represents the standard genetic baseline for these immune-related traits.
Typical risk of rheumatoid arthritis; Typical risk of IgA nephropathy.
Sample genotype: AG (Heterozygous)
This genotype means you carry one copy of the G allele, which tags the HLA-DRB1*0401 immune variant [1]. While a single copy does not elevate your rheumatoid arthritis risk as much as carrying two copies, it still represents a moderate increase in susceptibility, especially if other risk factors are present [1]. You also have a moderately higher risk of developing IgA nephropathy, an autoimmune kidney condition [2]. On the positive side, carrying this single G allele is associated with a lower risk of developing Parkinson's disease compared to non-carriers [3]. This profile represents a classic genetic trade-off between different neurological and autoimmune conditions.
Moderately higher risk of rheumatoid arthritis; Slightly higher risk of IgA nephropathy; Reduced risk of Parkinson's disease.
Sample genotype: GG (Homozygous)
This genotype means you carry two copies of the G allele, strongly indicating you are homozygous for the HLA-DRB1*0401 risk variant [1]. Clinical studies show this profile is associated with an estimated 6-fold increase in the risk of developing rheumatoid arthritis, particularly severe forms like rheumatoid vasculitis [1]. Additionally, this genotype is linked to a higher susceptibility to IgA nephropathy, a condition characterized by antibody buildup in the kidneys [2]. Conversely, this genetic profile is highly protective against Parkinson's disease, showing a significantly lower risk of onset and slower progression of symptoms [3]. Knowing this status can help you and your healthcare provider stay vigilant for early signs of joint or kidney inflammation.
Significantly higher risk of rheumatoid arthritis; Increased risk of IgA nephropathy; Significantly lower risk of Parkinson's disease.
Variants with shared genetic architecture
rs11751024 · HLA-DRB1 Gene · Chr 6 · Cholesterol and Immune Health
rs9271366 · HLA-DRB1 Gene · Chr 6 · Multiple Sclerosis Risk
rs477515 · HLA-DRB1 Gene · Chr 6 · Autoimmune and Vaccine Response
Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis.
Association between Parkinson's disease and the HLA-DRB1 locus.
Content updated August 2026.
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