rs6910071

badMag 6.5

This is a intron variant variant in the HLA-DRB1 gene.

Key Literature Trait Associations

Rheumatoid Arthritis

rs6910071 tags the HLA-DRB1 'shared epitope' alleles (most closely HLA-DRB1*04:01) — a common amino-acid motif at positions 70-74 of HLA-DRB1 that is strongly associated with rheumatoid arthritis (RA). The shared epitope alleles are particularly associated with seropositive RA (anti-CCP antibody positive), more severe joint disease, and extra-articular manifestations. The HLA-DRB1 locus explains roughly one-third of the total genetic risk for RA. The actual risk comes from the HLA-DRB1 protein sequence this SNP tags, which alters presentation of citrullinated self-proteins.

Stahl EA et al. “Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci.” Nature Genetics 42(6):508-514 (2010)

Allele G

OR 2.88

p 1.0e-299

Meta-analysis

Okada Y et al. “Genetics of rheumatoid arthritis contributes to biology and drug discovery.” Nature 506(7488):376-381 (2014)

Allele G

OR —

p —

N 103,638

Preliminary work

European and Asian

Verma A et al. “Phenome-Wide Association Study to Explore Relationships between Immune System Related Genetic Loci and Complex Traits and Diseases.” Plos One (2016)

Allele G

OR —

p 2.6e-9

N 5,923

Large GWAS

multi-ancestry (US biobank)

Polymyalgia rheumatica

rs6910071-G is associated with polymyalgia rheumatica (PMR), an inflammatory condition closely related to giant cell arteritis, with OR=1.5 (95% CI: 1.3–1.6) at p=1.3×10⁻¹⁰ in a study of 29,349 individuals of European ancestry. This association was identified through a phenome-wide scan for HLA-driven genetic phenotypes, and the overlap with the RA association signal is consistent with shared MHC immunogenetic risk between RA and PMR. PMR and RA share certain HLA haplotypes and inflammatory pathways, and rs6910071 likely tags the same MHC risk haplotype relevant to both conditions.

Mosley JD et al. “Identifying genetically driven clinical phenotypes using linear mixed models.” Nature Communications (2016)

Allele G

OR 1.50

p 1.3e-10

N 29,349

Large GWAS

European

Staphylococcus aureus seropositivity

rs6910071 was associated with variation in antibody epitope repertoire against a Staphylococcus aureus peptide in a population cohort study using phage-display immunoprecipitation sequencing (PhIP-seq) in 1,443 Dutch participants (p=4×10⁻¹⁰). The effect was reported as a z-score beta of 6.249, reflecting a large standardized shift in antibody reactivity. This finding is consistent with the SNP's location in the MHC/HLA region, which is well-established as the primary determinant of individual variation in adaptive immune responses, though this specific association is based on a single modest-sized study and requires replication.

Andreu-Sánchez S et al. “Phage display sequencing reveals that genetic, environmental, and intrinsic factors influence variation of human antibody epitope repertoire.” Immunity (2023)

Allele G

OR —

β 6.249

p 4.0e-10

N 1,443

Large GWAS

European (Dutch)

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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Research that mentions this SNP (1)

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Novel Rheumatoid Arthritis Susceptibility Locus at 22q12 Identified in an Extended UK Genome‐Wide Association Study

AssociationN=8,305Gisela Orozco et al.(2014)· Arthritis & Rheumatology

This extended UK genome-wide association study identified a novel rheumatoid arthritis susceptibility locus at 22q12 (rs1043099, P = 6.9 × 10⁻⁹, OR = 0.84) in 3,034 cases and 5,271 controls, and confirmed 16 previously known RA loci, strengthening evidence for genetic contributors to RA in the UK population.

rs6910071

Key Literature Trait Associations

Rheumatoid Arthritis

Polymyalgia rheumatica

Staphylococcus aureus seropositivity

GWAS Catalog Trait Associations (1)

Research that mentions this SNP (1)

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