For a century this was "wear and tear" — a joint used until it wore out. Then a scan of 4,800 people found its strongest signal in the immune genes, which is not where wear and tear lives.
Osteoarthritis of the knee is the loss of the cartilage that lets the joint move without pain. It is one of the commonest causes of disability in the world, and for most of the last century it was described as mechanical: a joint used until it wore out.
A genome-wide study in roughly 4,800 Japanese participants — a scan plus a replication set — found two positions associated with knee osteoarthritis. Both lie in the HLA class II/III region, and both reached genome-wide significance.
rs10947262, near HLA-DQA2, is one of them, at a combined P of 6.73 × 10⁻⁸.
That location is the finding. HLA class II genes exist to present fragments of protein to the immune system. If the strongest inherited signal for a "mechanical" disease sits there, then something immunological is involved in how a joint deteriorates — which is what the authors concluded, and which fits a growing body of work describing low-grade inflammation in osteoarthritic joints.
None of this displaces the obvious. Previous injury, joint alignment, occupation, age and body weight are the dominant risks, and weight is the one that can be changed: load on the knee is a multiple of body weight, so a small loss is a larger unloading than it sounds.
What the genetics adds is a mechanism running alongside the mechanics, not instead of them.
These positions come from a Japanese cohort. That is worth saying twice on a page about HLA, because HLA allele frequencies differ more between populations than almost any other part of the genome, and an association tagged in one population does not automatically hold in another.
Most of the evidence on this site comes from European-ancestry studies. This one does not, and the same caution runs in both directions.
Osteoarthritis is diagnosed from symptoms and examination, with imaging where it changes the decision. Treatment is weight, exercise — strengthening the muscles around the joint, which is counter-intuitive and works — pain relief, and replacement when the joint is worn past use.
No genotype enters any of that, and nothing here predicts who will need a new knee.
The source. Nakajima et al. (PLoS One 2010) conducted a genome-wide association study with replication in approximately 4,800 Japanese subjects, identifying rs7775228 (combined P = 2.43 × 10⁻⁸) and rs10947262 (combined P = 6.73 × 10⁻⁸) as associated with susceptibility to knee osteoarthritis. Both lie in a region containing HLA class II/III genes; the authors concluded that an immunological mechanism is implicated in the aetiology of osteoarthritis.
The variant recorded here. rs10947262, near HLA-DQA2 in the class II region. rs7775228 is not currently in this catalogue.
Interpretation. An HLA class II association is consistent with an antigen-presentation-dependent component to joint deterioration, and with the synovial inflammation observed in osteoarthritic joints. It does not make osteoarthritis an autoimmune disease, and the established risk factors — prior joint injury, malalignment, occupational loading, age and obesity — remain the dominant determinants.
Population. The discovery and replication samples were Japanese. HLA allele frequencies and linkage disequilibrium patterns differ substantially between populations, so neither the effect size nor the tagging relationship should be assumed to transfer.
Clinical boundary. Knee osteoarthritis is diagnosed clinically, with radiography where it alters management. Genotype has no role in diagnosis, prognosis, or the choice between conservative management and arthroplasty.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Knee Osteoarthritis comes down to these specific, well-studied positions — not a diagnosis.
Because deterioration of a joint appears to involve inflammation as well as load. The scan found its strongest signal in the HLA class II/III region, which exists to present protein fragments to the immune system. That does not make osteoarthritis an autoimmune disease — it means a second mechanism runs alongside the mechanical one.
Weight and exercise, in that order of leverage. Load through the knee is a multiple of body weight, so a modest loss unloads the joint more than it sounds like it would. Strengthening the muscles around a painful joint feels wrong and is one of the better-supported treatments there is.
Not automatically. HLA allele frequencies differ between populations more than almost any other part of the genome, so an HLA association found in one population has to be re-established in another. Most evidence on this site has the mirror-image problem, being European.
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