Approved research

Investigating the genomics of post-traumatic osteoarthritis (PTOA)

Lay summary

We want to understand how someone's genes affect their risk of developing knee osteoarthritis (OA) after a knee injury, so called post-traumatic OA (PTOA), by identifying those with a previous knee injury and knee OA (PTOA) in UK Biobank (~1000-2000 cases). We will ask: * whether known 'osteoarthritis genes' are also associated with PTOA; * how much PTOA risk can be explained by these genes, and how much of the risk is different; * how well can we identify cases of PTOA using different approaches. This will help us to find the best way to look for PTOA genes internationally in the future in a large international working group 'the Genetics of Osteoarthritis consortium'. Osteoarthritis is the most common form of arthritis, affecting 8.5 million people in the UK. Significant knee injuries are a major risk factor for knee OA. Some think PTOA is different from 'usual OA', but we don't know this for sure. Not all OA gets worse - some stays the same or get better. This is a challenge when running clinical trials or treating the condition. Understanding genes or pathways associated with worsening PTOA after a knee injury (or protection from it) will help us understand OA better. ~60% of a person's risk of knee OA is inherited. Large-scale OA studies have already found lots of genes and pathways, but have not yet led to a breakthrough in treatment. Recently ~70 genes which contribute to OA risk were found in UK Biobank, most with very small effects. We will use this knowledge, testing if these same genes have a greater role in PTOA, or if there are other important genes. The project will last for 3 years. We believe finding new tests and treatments for OA is of high public interest. This is a very common condition with huge social and economic cost. The main reason for joint replacement, there are currently no medical treatments which prevent or slow it down. Genetic tests could be included in an individual risk score which helps us to pick out in clinic those at greatest risk of PTOA at the time of injury. This would improve the treatment of people with joint injury and enable clinical trials. We will discover if PTOA is the same, or different, to usual OA - important in us making progress. We might find new pathways which help us to develop new treatments in OA as a whole.