Genes linked to Paget's disease of bone

Three genetic regions have been linked for the first time to a bone disease called Paget's disease by an international research team. Genes in these regions and four others identified in a previous study explain about 13 percent of the risk of developing the disease.

Professor Stuart Ralston, Arthritis Research UK professor of rheumatology at the University of Edinburgh, who led the study, said: 'The effect of these (genes) is large, and together they considerably increase the risk of developing the condition'.

Scientists carried out genome wide association studies (GWAS) to identify the location of genetic regions linked to Paget's. GWAS is where scientists compare the DNA from many people with a disease like Paget's (cases) against DNA from people without the disease (controls).

The researchers compared the genomes of 2,215 cases with 4,370 controls. They excluded data from people with a mutation in the gene SQSTM1, as this gene is already strongly linked to Paget's disease and they wanted to uncover other mutations. They also excluded people who weren't of European descent, as Paget's disease is most common in Europe.

As well as finding these three new genetic regions, the researchers also confirmed other genetic regions, which they had previously identified using a similar method, were linked to Paget's disease.

The scientists hope their findings will - in the future - enable genetic testing to identify people at risk of developing the disease, and earlier diagnosis and treatment.

'Their effects are so powerful that they could be of real value in screening for risk of the disease. This is important since we know that if treatment is left too late, then irreversible damage to the bones can occur', said Professor Ralston.

Professor John Walsh, another author on the paper said: 'When you have Paget's disease, and it's diagnosed, sometimes you already have quite a lot of bone damage, and deformity, and pain and then of course it's much less satisfactory treating that as getting in early and preventing the disease from developing'.

The scientists plan to study how these genetic regions are contributing to the disease.

Paget's disease is more common in the UK than anywhere else in the world, affecting up to one million people. It mainly affects older people whose bones develop and renew themselves abnormally, often leading to enlarged and malformed bones.

The study involved scientists from the UK, Italy, Belgium, Australia, Holland and Spain and was published in the journal Nature Genetics.