Public Release: 

New osteoarthritis genes discovered, paving way for new therapies

In the largest study of its kind, nine novel genes for osteoarthritis have been discovered by scientists from the University of Sheffield and their collaborators

University of Sheffield

  • University of Sheffield scientists discover nine novel genes for osteoarthritis
  • 10 million people suffer from osteoarthritis in the UK - a degenerative disease in which a person's joints become damaged, stop moving freely and become painful
  • Findings could open the door to new targeted therapies
  • Osteoarthritis is a leading cause of disability worldwide

In the largest study of its kind, nine novel genes for osteoarthritis have been discovered by scientists from the University of Sheffield and their collaborators.

Results of the study, published today (19 March 2018) in Nature Genetics, could open the door to new targeted therapies for this debilitating disease in the future.

Ten million people in the UK suffer from osteoarthritis, a degenerative disease in which a person's joints become damaged, stop moving freely and become painful. Osteoarthritis is the most prevalent musculoskeletal disease and a leading cause of disability worldwide.

There is no treatment for osteoarthritis. The disease is managed with pain relief and culminates in joint replacement surgery, which has variable outcomes.

In the largest study of its kind, scientists from the University of Sheffield and their collaborators investigated the genetics behind osteoarthritis, as well as the diseases and traits that are linked to it.

To understand more about the genetic basis of osteoarthritis, the team studied 16.5 million DNA variations from the UK Biobank resource. Following combined analysis in up to 30,727 people with osteoarthritis and nearly 300,000 people without osteoarthritis in total, scientists discovered nine new genes that were associated with osteoarthritis, a significant breakthrough for this disease.

Ms Eleni Zengini, joint first author from the University of Sheffield and Dromokaiteio Psychiatric Hospital in Athens, said: "These results are an important step towards understanding the genetic causes of osteoarthritis and take us closer to uncovering the mechanisms behind the disease. Once we know that, it opens the door to developing new therapies for this debilitating disease."

Researchers investigated the role of the nine new genes in osteoarthritis, by studying both normal cartilage and diseased cartilage from individuals who had a joint replacement.

The team looked for genes that were active in the progression of the disease by extracting the relevant cells from healthy and diseased tissue. They examined the DNA signatures, looking for differences between subjects with osteoarthritis to those without.

Of the nine genes associated with osteoarthritis, researchers identified five genes in particular that differed significantly in their expression in healthy and diseased tissue. The five genes present novel targets for future research into therapies.

Professor Eleftheria Zeggini, senior author from the Wellcome Sanger Institute, said: "Osteoarthritis is challenging to study because the disease can vary among people, and also between the different joints affected, for example knee, hip, hand and spine. Using data from the UK Biobank resource, we have undertaken the largest genetic study of osteoarthritis to date and uncovered nine new genes associated with the disease."

The team also explored genetic correlations between osteoarthritis and obesity, bone mineral density, type 2 diabetes and raised blood lipid levels.

Researchers applied a statistical technique, known as causal inference analysis, to uncover which traits and diseases cause osteoarthritis, and which do not.

Within the limits of their study, scientists discovered that type 2 diabetes and high levels of lipids in the blood do not have causal effects on osteoarthritis, but reaffirm that obesity does.

Dr Konstantinos Hatzikotoulas, joint first author from the Wellcome Sanger Institute, said: "Using genetic data, we have shown that type 2 diabetes and increased blood lipid levels do not appear to be on the causal path to osteoarthritis. We also reconfirmed that obesity is on the causal path to osteoarthritis."

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