Rheumatoid arthritis: largest study yet yields risk gene haul

The largest genetic study of rheumatoid arthritis (RA) to date has found an additional 42 disease-associated locations in the genome. Published in Nature, the authors claim that these sites might offer insights in repurposing existing drugs to treat RA.

Researchers from institutions across seven countries analysed genetic data from 100,000 people — 29 percent with RA and 71 percent healthy controls — looking at ten million different genetic sites in each. By comparing the healthy DNA against those with RA, the authors could see whether any particular genetic difference is associated with the disease.

Each of these sites, or SNPs (single nucleotide polymorphisms), is a particular location in our DNA that is known to differ between people by one 'letter' or base. By looking at which genes the disease-associated SNPs occur in or near to, it might be possible to find biological processes that contribute towards diseases.

Beyond the traditional genome-wide association studies (GWAS) used to measure SNPs, this study used a number of different laboratory and data-mining experiments to get extra information from their genetic data.

In addition to finding the 42 RA-associated SNPs (bringing the total of such known 'risk' sites up to 101), this study aimed to use these novel techniques to use the genetic data as a resource to find known drugs which might be useful for treating RA.

The researchers used a database of drug targets to find a list of genes for which there is an approved or experimental drug that targets the protein that the gene encodes. This list was then compared to the list of genes that the RA risk-SNPs occur close to, along with genes that they interact with.

This analysis produced 27 genes that are already the targets of existing RA drugs, which suggests that these genetic techniques are indeed able to find suitable genes to target therapeutically. Furthermore, other genes which are targeted by drugs used to treat other diseases were also revealed, including a number of anti-cancer drugs, raising the possibility these drugs might also be useful in treating RA.

'This [study] almost doubles the number of previously-known risk regions and adds a significant amount to the current knowledge and understanding of the genetic basis of this condition', said Professor Alan Silman, medical director of Arthritis Research UK.

'In addition, the results of this work have identified similarities with some other conditions which suggests that evaluation of existing treatments could be beneficial and may lead to new and improved therapies for the half a million people currently living with rheumatoid arthritis'.