Genome-wide association study for osteoarthritis

The genome-wide association study by Eleftheria Zeggini and colleagues (Sept 1, p 815)

identified several significant susceptibility loci for osteoarthritis. Although the findings are promising, we have several concerns about their interpretation and generalisablility.

First, the conclusion that the FTO gene exerts its effect on osteoarthritis through obesity could be inaccurate, since it is hard to be sure about the direction of causation between obesity and osteoarthritis. Of various risk factors, obesity is one of the most important for osteoarthritis, especially that in weight-bearing joints.

However, it is not possible to ascertain whether obesity causes osteoarthritis or whether obesity is caused by an osteoarthritis-induced decrease in activity. Similarly, we cannot determine the direction of causation between the FTO gene and osteoarthritis.

Second, the findings of this study were restricted to people of European descent and might not be generalisable to other ethnic groups. Osteoarthritis is a degenerative disorder with multiple causative factors, the prevalence and severity of which vary across racial and ethnic groups.

Furthermore, the weights of genetic and environmental factors also differ geographically. Therefore, further research is needed to investigate the potential mechanisms underlying racial or ethnic differences.

We declare that we have no conflicts of interest.