A chronic inflammatory arthritis of the spine and pelvis, driven mainly by HLA-B27 — three separate studies have also found 6 other variants, on this page, each independently.
Ankylosing spondylitis (AS) is a common, highly heritable form of chronic inflammatory arthritis that primarily affects the spine and pelvis, causing pain and stiffness that can progress to fused vertebrae over years. It affects roughly 5 per 1,000 adults of European descent. The single strongest genetic risk factor by far is a specific HLA variant, HLA-B27 — not itself a simple SNP this site's catalogue captures — but three separate genome-wide studies have also found other, smaller contributors, six of which are on this page.
A 2011 study of European-ancestry participants found that variants in ERAP1 (not on this page) only raise AS risk in people who also carry HLA-B27 — evidence that AS involves a specific mechanism: how the body trims protein fragments (peptides) before presenting them to the immune system on HLA-B27 itself. That same study identified three variants "convincingly associated" with AS: in RUNX3, LTBR-TNFRSF1A, and IL12B. This page carries two of those three — rs11249215 (RUNX3) and rs11616188 (LTBR-TNFRSF1A).
A larger 2013 study genotyped 10,619 people with AS against 15,145 controls at immune-related sites specifically, and found 13 new risk loci. It highlighted that two of the AS-associated regions encode aminopeptidases — enzymes that trim those same peptides — involved in processing before HLA-B27 presentation. This page's rs10045403, in ERAP2, sits directly in that theme; the same study's rs17765610 (BACH2) and rs35164067 (TYK2) are two more of its 13 new loci. BACH2 recurs across several other autoimmune conditions on this site, including autoimmune thyroid disease and primary sclerosing cholangitis.
A separate 2011 study in Han Chinese participants found exactly two new loci in that population: one near EDIL3/HAPLN1 (not in our catalogue) and one within ANO6 at chromosome 12q12 (rs17095830), on this page. The study noted that both of its new loci "implicate genes related to bone formation and cartilage development" — a plausible fit for a disease that progressively fuses spinal joints.
2025-10-30 · A Multitrait Analysis of Genome-Wide Association Study Reveals the Shared Genetic Architecture Between Inflammatory Bowel Disease and Ankylosing Spondylitis. Mediators of Inflammation. 2025. DOI:10.1155/mi/4012195
Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) frequently co-occur clinically, and this study tested whether that reflects genuine shared genetics. It found significant positive genetic correlations between IBD and AS overall (rg=0.252, P=3.78e-6), and separately for Crohn's disease and AS (rg=0.268) and ulcerative colitis and AS (rg=0.171) -- both inflammatory bowel subtypes correlate with AS, Crohn's more strongly. Multitrait analysis and cross-phenotype association methods identified 24 pleiotropic SNPs across the three trait-pair comparisons, and gene-level analysis converged on 8 shared functional genes. Shared genetic enrichment was found specifically in lung, spleen, small intestine and whole blood tissue, and in T cell and B cell populations -- a coherent immune-tissue story. The genuinely notable finding, reported honestly rather than glossed over, is that bidirectional Mendelian randomization found no causal relationship between the two conditions in either direction -- the genetic correlation reflects shared underlying biology and pleiotropic loci, not one condition genetically causing the other. This is a useful, honest distinction: real shared genetic architecture without causation. This site's ankylosing spondylitis page carries 7 variants; this entry documents the shared-architecture finding as context rather than new named variants, since the abstract does not specify the 8 shared gene names individually.
Ankylosing spondylitis is diagnosed by a rheumatologist using symptoms, imaging (X-ray or MRI of the sacroiliac joints), and HLA-B27 testing — not by any variant on this page. HLA-B27 itself, the dominant genetic risk factor, is a different kind of genetic marker than the six SNPs listed here and is not part of this page's variant set.
The six variants here are each individually much weaker contributors than HLA-B27, found through genome-wide studies designed to look past it. None is used clinically to diagnose AS or guide treatment.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Ankylosing Spondylitis comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 7 of 7 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
A common, highly heritable chronic inflammatory arthritis that primarily affects the spine and pelvis, causing pain and stiffness that can progress to fused vertebrae over years. It affects roughly 5 per 1,000 adults of European descent.
No. HLA-B27 is the single strongest genetic risk factor for AS by far, but it is a different kind of genetic marker than the six SNPs on this page and isn't part of this page's variant set.
Three separate genome-wide studies found them independently, in European and Han Chinese populations. Two (ERAP2, and HLA-B27 itself, off this page) point to how the body processes peptides before immune presentation; one (ANO6) points to bone and cartilage biology.
No. AS is diagnosed by a rheumatologist using symptoms, imaging, and HLA-B27 testing, not by any variant listed here.
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