In the largest genetic study to date on osteoarthritis, nine new genes for the disease have been discovered by scientists at the University of Sheffield, including five directly involved in the worsening of the disease. The results of the study, published in Nature Genetics, could open the door to developing new targeted treatments for this debilitating disease.
To better understand the genetic basis of osteoarthritis, the team studied 16.5 million DNA variations from the UK Biobank DNA Data Bank. With a combined analysis of 30,727 people with osteoarthritis and nearly 300,000 people without osteoarthritis, scientists discovered nine new genes associated with the disease, a significant breakthrough for the disease.
The team also explored the genetic correlations between osteoarthritis and obesity, bone mineral density, type 2 diabetes, and high blood lipid levels.
Osteoarthritis is the most common musculoskeletal disease and one of the leading causes of disability in the world. Its links with various associated diseases, common at this age (diabetes, hypercholesterolemia, obesity), are not well understood.
There is currently no definitive cure, mainly symptomatic treatments of pain and inflammation during outbreaks. Articular replacement surgery usually comes to end a more or less prolonged and rather painful evolution over several years.
Within the scope of this study, scientists have found that type 2 diabetes and high levels of cholesterol in the blood have no causal effects on osteoarthritis, but reaffirm that of obesity.
The team looked for genes that were active in the progression of the disease by extracting DNA from healthy and diseased synovial cells and comparing them according to the technique. Among the nine genes associated with osteoarthritis, the researchers identified five genes in particular that differed significantly in their expression in healthy and diseased tissues. The five genes present new targets for the development of new treatments.
According to Eleni Zengini of the University of Sheffield and co-author of the study: “These results are an important step in understanding the genetic causes of osteoarthritis and bringing us closer to the discovery of the true mechanisms of the disease. This opens the door to the development of new specific treatments for this disabling disease. “