Why did I get arthritis? Is it genetic?
Orthopedic specialists, primary care physicians, family members, and patients all can relate anecdotes about reports and observations of familial patterns of osteoarthritis. A common question is, “Is my arthritis genetic?” A new genetic variant study of millions of patients recently published in the journal Nature identified 962 independent gene variants tied to osteoarthritis(1). If you have one of these gene variants you may be at a higher risk, although the individual tests are not yet commercially available. The research provides some promising clues about the genetic basis of osteoarthritis and potential therapeutic targets.
The researchers conducted a genome-wide association study (GWAS), a method that scans the DNA of huge groups of people to spot genetic differences linked to diseases. They compared up to 489,975 individuals with osteoarthritis to 1,472,094 without it, across diverse ancestries like European, East Asian, and African American. This giant sample size—almost 2 million in total—gave them the power to detect subtle genetic signals that smaller studies might miss.
This study used a cutting-edge process called single-cell multiomics data from a human skeletal development atlas. This high-tech approach looks at gene activity in individual cells during early skeletal growth (5-11 weeks after conception). What they found was that osteoarthritis-related genes are active in early skeletal development, particularly in cartilage cells (chondrocytes). This suggests that issues in how joints form early in life may contribute to osteoarthritis later.
There were 700 primary “effector genes” that drive arthritis. These genetic variants, some having mild and some having large effects, are involved in signaling pathways that control bone and cartilage development, extracellular matrix organization, and circadian rhythm and glial cell processes. The circadian rhythm and glial cell process findings are newly linked to arthritis.
The circadian rhythm linkage is interesting. Circadian rhythm is your body’s internal 24-hour clock, regulating processes like sleep, metabolism, and hormone release. The finding in this study that the daily internal clock may play a role in arthritis suggests that disruptions in the body’s daily clock may influence joint health. For example, irregular sleep patterns or shift work could affect cartilage maintenance or inflammation, contributing to arthritis. This connection implies that arthritis isn’t just about physical wear and tear but also about how the body’s timing mechanisms regulate joint tissues. The circadian rhythm link may also partially explain why some patients struggling with arthritis symptoms have morning stiffness.
Glial cells are non-neuronal cells primarily found in the nervous system, where they support nerve cells by providing nutrients, insulation, and immune defense. They’re not typically associated with joints, making this finding surprising. Glial-like cells might regulate inflammation or tissue repair in joints, similar to their role in the nervous system. Their involvement in arthritis could explain chronic pain or inflammation in affected joints, offering a new angle on why arthritis is so painful. This link might lead to treatments targeting glial-like pathways to reduce joint inflammation or pain, improving quality of life for osteoarthritis patients.
The findings in this study are interesting but no clear easy treatments are yet available. Some of the findings in the study connect to drugs already available, which could be reused to help treat osteoarthritis sooner and limit progression of the disease. While predicting who’ll get the disease is still tricky, this study is a big step toward better treatments.
References:
- Hatzikotoulas K. et al. Translational genomics of osteoarthritis in 1,962,069 individuals. Nature. 2025 Apr 9. doi: 10.1038/s41586-025-08771-z. Epub ahead of print. PMID: 40205036.
