What you carry at this position in your DNA and what research says about it.
Multiple Sclerosis Risk: 8/10 evidence, 33 publications.
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Sample genotype (not yours): A/A
Significantly Higher Multiple Sclerosis Risk
Carrying two copies of the A allele is associated with a 3 to 6 fold increase in the risk of developing multiple sclerosis. It also increases susceptibility to other autoimmune conditions like lupus.
What this genotype means: Significantly increased risk of multiple sclerosis; Increased susceptibility to systemic lupus erythematosus; Reduced risk of neuromyelitis optica.
Sample genotype (not yours): A/G
Increased Multiple Sclerosis Risk
Carrying one copy of the A allele is associated with an approximate 3-fold increase in multiple sclerosis risk. It also moderately increases susceptibility to lupus.
What this genotype means: Increased risk of multiple sclerosis; Moderately increased susceptibility to systemic lupus erythematosus; Reduced risk of neuromyelitis optica.
Sample genotype (not yours): G/G
Typical Multiple Sclerosis Risk
Carrying two copies of the G allele is associated with typical, baseline risk for multiple sclerosis and lupus. This is the most common genetic profile globally.
What this genotype means: Typical baseline risk of multiple sclerosis; Typical baseline risk of systemic lupus erythematosus; Typical baseline risk of neuromyelitis optica.
Gene function and biological role
Gene Function: The HLA-DRA gene encodes the alpha chain of the HLA-DR antigen-presenting complex, a critical component of the human immune system. This complex is expressed on the surface of immune cells, where it presents foreign peptides to T cells to initiate immune responses. Genetic variation in this region is heavily implicated in susceptibility to various autoimmune disorders [1]. The gene is located within the major histocompatibility complex on chromosome 6, a region known for its high genetic diversity and strong linkage disequilibrium [2]. Variations in HLA-DRA expression levels can significantly alter immune tolerance and self-recognition pathways [3].
Variant Impact: This downstream variant acts as a highly reliable genetic surrogate or tag for the HLA-DRB1*1501 immune haplotype [4]. The presence of the minor A allele at this locus is strongly correlated with elevated expression of several major histocompatibility complex class II genes, including DRB1, DRB5, and DQB1 [3]. This increased expression is thought to alter immune cell activation and susceptibility to autoimmune attacks [3]. While it significantly elevates the risk of multiple sclerosis, it has also been shown to have protective effects against other neuroinflammatory conditions like neuromyelitis optica [5].
Key Insight: This variant acts as a genetic surrogate for the HLA-DRB1*1501 haplotype, which is the single strongest genetic risk factor for multiple sclerosis. Interestingly, the same allele that increases multiple sclerosis risk actually reduces the risk of developing neuromyelitis optica.
Location: HLA-DRA. Chromosome 6 · 6p21.32 · 32.4 Mb
Estimated prevalence by population
Global 1.1%; European 1.9%; African 0.2%; East Asian < 0.1%; South Asian < 0.1%; Americas 0.5%; Ashkenazi < 0.1%; Finnish 1.6%; Middle Eastern 0.3%; Amish 0.7%.
Estimated AA genotype frequency.
Global 16.6%; European 24.0%; African 8.9%; East Asian 0.7%; South Asian 3.8%; Americas 13.4%; Ashkenazi 4.3%; Finnish 22.4%; Middle Eastern 10.9%; Amish 15.8%.
Estimated AG genotype frequency.
Global 82.3%; European 74.1%; African 90.9%; East Asian 99.3%; South Asian 96.1%; Americas 86.1%; Ashkenazi 95.7%; Finnish 76.0%; Middle Eastern 88.8%; Amish 83.4%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Immunity & Inflammation
Autoimmune Diseases
Multiple Sclerosis. Evidence: 8/10. Source: PMID 17660530. ~3-6x Higher Risk.
Lupus. Evidence: 3/10. Source: PMID 19387463. Increased Risk.
Neuromyelitis Optica. Evidence: 3/10. Source: PMID 20591987. ~43% Lower Risk.
Showing effects for A/G genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 17660530. ~3x Higher Risk.
Showing effects for G/G genotype
Multiple Sclerosis. Evidence: 8/10. Source: PMID 17660530. Typical Risk.
Lupus. Evidence: 3/10. Source: PMID 19387463. Typical Risk.
Neuromyelitis Optica. Evidence: 3/10. Source: PMID 20591987. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Inheriting two copies of the A allele strongly correlates with the HLA-DRB1*1501 immune haplotype, which is the primary genetic driver of multiple sclerosis susceptibility [1]. This genotype is associated with up to an 8-fold increase in the expression of the DRB1 gene, potentially leading to hyper-reactive immune responses [2]. Research indicates that this genetic profile significantly elevates the risk of multiple sclerosis, with some studies estimating a 3 to 6 fold increase in susceptibility [3]. It is also associated with a higher likelihood of other autoimmune conditions, such as systemic lupus erythematosus [4]. However, this genotype appears to offer a protective effect against neuromyelitis optica, a distinct neuroinflammatory disorder [5]. Maintaining adequate vitamin D levels is often discussed in clinical literature as a potential environmental modifier for individuals carrying this risk profile [6].
Significantly increased risk of multiple sclerosis; Increased susceptibility to systemic lupus erythematosus; Reduced risk of neuromyelitis optica.
Sample genotype: AG (Heterozygous)
Carrying a single copy of the A allele serves as a genetic marker for the HLA-DRB1*1501 haplotype, a well-established risk factor for autoimmune diseases [1]. This heterozygous genotype is associated with intermediate to high expression levels of key antigen-presenting genes in the immune system [2]. Clinical studies consistently demonstrate that individuals with this genotype have roughly a 3-fold higher risk of developing multiple sclerosis compared to non-carriers [3]. There is also a documented association with an increased risk of systemic lupus erythematosus [4]. Conversely, the presence of this allele is linked to a lower risk of neuromyelitis optica, demonstrating a complex role in neuroinflammatory pathways [5]. Environmental factors, particularly vitamin D status and sunlight exposure, are frequently studied for their potential to modulate these genetically driven autoimmune risks [6].
Increased risk of multiple sclerosis; Moderately increased susceptibility to systemic lupus erythematosus; Reduced risk of neuromyelitis optica.
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele represents the baseline genetic profile for the majority of global populations. This genotype does not carry the HLA-DRB1*1501 risk haplotype, meaning there is no genetically elevated risk for multiple sclerosis from this locus [1]. Levels of HLA-DRB1 gene expression remain at typical baseline levels, avoiding the immune hyper-reactivity associated with the risk variant [2]. Large-scale genome-wide association studies confirm that individuals with this genotype have a standard, non-elevated risk of developing multiple sclerosis [3] and systemic lupus erythematosus [4]. However, because this genotype lacks the protective effect of the A allele, the risk for neuromyelitis optica remains at the typical population baseline rather than being reduced [5]. Overall, this genetic profile is considered highly favorable for avoiding major autoimmune susceptibilities linked to this region.
Typical baseline risk of multiple sclerosis; Typical baseline risk of systemic lupus erythematosus; Typical baseline risk of neuromyelitis optica.
Variants with shared genetic architecture
rs2395185 · HLA-DRA Gene · Chr 6 · Autoimmune Disease Risk
rs3177928 · HLA-DRA Gene · Chr 6 · IgA Vasculitis Risk
rs6903608 · HLA-DRA Gene · Chr 6 · Hodgkin Lymphoma Risk
Risk alleles for multiple sclerosis identified by a genomewide study.
HLA-DRB1*1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica.
Content updated August 2026.
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