Third genetic link to osteoarthritis discovered
26 August 2011
The preliminary stage of the original arcOGEN study, funded by Arthritis Research UK, compared the genomes of 3177 people with osteoarthritis with 4894 people from the general population and looked at 600 000 gene variants. At that level of detail, the researchers were unable to identify any new genes. By including data from the 1000 Genomes Project, the new study was able to scan for 7.2 million variants; it revealed the association of a variant located within a gene called MCF2L, without requiring any new sequencing to be carried out.
Dr Eleftheria Zeggini, senior author from the Wellcome Trust Sanger Institute, said: "By using the 1000 Genomes data to add value to our original genome-wide association scan for osteoarthritis, we have uncovered a disease-associated gene that had previously remained hidden.
"We were able to analyse our results in greater detail and zoom in on variants that we hadn't been able to identify before. We hope that this approach and our findings will help to improve our biological understanding of this very painful disease."
Osteoarthritis is a complex condition and researchers have found it difficult to identify the genes that are involved. Only two genes have been linked with the disease so far in European populations - GDF5 and a signal from a region on chromosome 7.
The newly identified variant is located in a gene on chromosome 13 called MCF2L, which regulates a nerve growth factor (NGF). It has been reported that when people with osteoarthritis in the knee are treated with a humanised monoclonal antibody against NGF, they experience less pain and show improved movement. This suggests that MCF2L is involved in the development of osteoarthritis and provides a new focus for future research.
To confirm this association, the team worked with international collaborators to investigate 19 041 people with arthritis and 25 504 people without. A number of centres across Europe collaborated by screening people in Iceland, Estonia, the Netherlands and the UK for the newly identified variant in order to corroborate the association.
"The discovery of this MCF2L variant suggests a possible genetic link to the finding that regulating NGF is important in knee osteoarthritis, and is supported by the fact that the variant is more strongly associated with knee osteoarthritis than hip osteoarthritis in the study," says Aaron Day-Williams, first author of the study from the Sanger Institute. "We hope the identification of this variant will lead to further insights into the biological processes at work and offer potential treatment targets."
The study's findings are based on the work of the arcOGEN Consortium, which was funded by Arthritis Research UK.
Image: Arthritic hip. Credit: J M Wilkinson
Reference
Day-Williams AG et al. A variant in MCF2L is associated with osteoarthritis. Am J Hum Genet 2011 [epub].