GENETIC risk scores for knee osteoarthritis do not predict disease progression, new cohort study reveals. Researchers analyzing data from the IMI-APPROACH cohort found that while certain genetic variants are associated with the presence of knee osteoarthritis (OA), these same markers do not forecast how the disease will evolve over time.
The study examined 297 individuals with knee OA, following them over 24 months to assess structural and symptomatic disease progression. Key outcome measures included changes in minimum joint space width (minJSW), increasing pain as measured by the KOOS scale, and radiographic OA progression assessed by Kellgren-Lawrence scoring.
Researchers focused on 30 previously identified single nucleotide polymorphisms (SNPs) that had been linked to the presence of OA, investigating their relationship to disease worsening. Surprisingly, none of these known OA-related SNPs, either individually or combined into a polygenic risk score, were associated with progression of the disease.
However, the genome-wide association analysis yielded significant findings. Nineteen SNPs not previously linked to OA presence were associated with narrowing of joint space, suggesting potential new genetic drivers of disease progression. Ten of these were located near protein-coding genes including PLCL2, CDYL2, and NTNG1, while others were located in or near long non-coding RNAs (lncRNAs), pointing to novel biological pathways that may influence structural joint decline.
These findings underscore the complex nature of knee OA and highlight the disconnect between genetic predisposition to disease onset and the molecular factors that drive disease worsening. While the previously known risk variants inform who may develop OA, they do not appear to predict which patients will experience structural deterioration or worsening symptoms over time.
The study demonstrates the utility of integrating multiple bioinformatics tools to prioritize new genetic biomarkers, even in moderately sized cohorts. It opens new avenues for personalized medicine in OA by identifying progression-specific markers that warrant further investigation.
Reference:
Bentvelzen ML et al. Genetic markers for knee osteoarthritis presence are not associated with disease progression – data from the IMI-APPROACH cohort. PLoS One. 2025;20(6):e0325819.
