Today investigators have revealed a new gene making it only the third to be identified for this painful and debilitating disease connected with osteoarthritis. The disease affects over 40% of people aged 70 years and over.
The disease-associated variant, in the gene MCF2L, was found when Wellcome Trust Sanger Institute investigators used information from the 1000 Genomes Project to increase the power of their genome-wide association scan. The initial stage of the original arcOGEN investigation, funded by Arthritis Research UK, compared the genomes of 3,177 individuals with osteoarthritis with 4,894 people from the general population and looked at 600,000 variants.
Even though the full investigation had yet to be published, no new genes were identified at that level of detail. The new study was able to scan for 7.2 million variants and revealed the connected of MCF2L with osteoarthritis without needing any new sequencing to be carried out, by imputing the information from the 1000 Genomes Project.
Dr Eleftheria Zeggini, senior author from the Sanger Institute explained:
“By using the 1000 Genomes Project information 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 analyze 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.”
As osteoarthritis is a complicated condition investigators have found it hard to identify its genes. Just two loci have been discovered to date in European populations – GDF5 and a signal from a region on chromosome 7.
The newly identified gene, MCF2L, is found on chromosome 13 and regulates a nerve growth factor (NGF). When those with osteoarthritis in the knee are treated with a humanized monoclonal antibody against NGF, they experience reduced pain and show improvement in their movement, it has been reported. Suggesting that MCF2L is involved in the development of osteoarthritis and gives a new focus for investigations in the future.
The team worked with international collaborators to research 19,041 individuals with arthritis and 25,504 without in order to make sure that the variant of MCF2L is linked with the development of osteoarthritis. For the newly identified variant to corroborate the association, numerous centers throughout Europe worked together by screening people in Iceland, Estonia, the Netherlands and the UK.
Aaron Day-Williams, first author of the study from the Sanger Institute says:
“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 linked with knee osteoarthritis than hip osteoarthritis in the investigation.
We hope the identification of this variant will lead to further insights into the biological processes at work and offer potential treatment targets.”
The investigation’s discoveries are based on the work of the arcOGEN Consortium, which has been funded by Arthritis Research UK and is an essential supporter of research in this area.
Alan Silman, Medical Director of Arthritis Research UK explains:
“Osteoarthritis is a complicated disease with many genetic causes. However, it has proved very difficult to discover the genes involved and help us to identify potential areas of treatment.
We are delighted that investigators at the Sanger Institute have been able to identify a new gene connected with this painful condition and offer new lines of research for possible treatments. We are also excited that employing the technique of using the 1000 Genomes Project data to investigate genetic associations in far greater depth could reveal even greater insights into this debilitating disease.”
Written by Grace Rattue