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Major new study finds clues to the genetic causes of osteoarthritis

Published on 03 July 2012

Osteoarthritis sufferer Terry Lawrence and family
UK scientists have discovered more genetic regions associated with the cause of osteoarthritis. Researchers from nine institutions across the UK have described the findings as a significant breakthrough in understanding the genetic risk factors that cause the disease.

Publishing their findings in The Lancet today (July 3) the Arthritis Research UK-funded arcOGEN consortium has highlighted eight genetic regions linked to the development of osteoarthritis. Previously only three osteoarthritis genetic regions had been identified.

Several of the genetic regions encompass genes that are known to regulate how joints are made and then maintained, making them excellent osteoarthritis candidate gene. Another genetic region contains a gene involved in the regulation of body weight, which is a strong risk factor for osteoarthritis.

The £2.2million project is the world’s biggest ever-genome wide study into osteoarthritis, comparing the genetic differences of 7,400 patients with severe osteoarthritis with 11,000 healthy volunteers. The results were then replicated in over 7,000 OA individuals and 43,000 control individuals, from four European collaborating partners.

Osteoarthritis affects around 40 per cent of people over the age of 70, a total of 8 million people in the UK, causing pain and disability. There is currently no cure for the condition. Treatments for early osteoarthritis are limited to non-surgical options such as painkillers and physiotherapy until joint replacement becomes a viable option. Osteoarthritis is a complex disorder with both environmental and genetic causes. It is estimated that about 50 per cent of an individual’s risk of developing osteoarthritis is due to inherited genetic factors.

Professor John LoughlinPrincipal investigator of arcOGEN John Loughlin, professor of musculoskeletal research at Newcastle University, said: “We know that osteoarthritis runs in families and that this is due to the genes that people pass on, rather than their shared environment. In this study we were able to say with a high degree of confidence which genetic regions are the major risk factors for developing osteoarthritis: the first time that this has been possible for this common yet complex disease. It’s an important first step.”

Two of the novel regions are close to genes that immediately suggest clinical implications for osteoarthritis. One, CHST11, affects cartilage proteoglycan (proteins in the cartilage modified with sugar chemicals) and changes in proteoglycan are an active area of development of new treatments for osteoarthritis. A second gene, PTHLH, is the basis for recently developed parathyroid hormone-based treatments for osteoporosis. The research team suggest a next step would be to explore whether these compounds may also be effective in osteoarthritis.

Dr Ele Zeggini, first and senior co-author on the research from the Wellcome Trust Sanger Institute, said: “We discovered eight new regions that might contribute to osteoarthritis, several of which might be involved in the development, production or maintenance of healthy cartilage. They provide a fascinating insight into the processes that could contribute to this disease and – importantly – our list of genetic culprits also helps us to begin to pick apart this challenging disease, opening a door which could lead to treatments targeted to specific types of osteoarthritis.”

Professor Alan SilmanMedical director of Arthritis Research UK Professor Alan Silman said: “There is no cure for osteoarthritis yet it affects millions of people around the world. For 60 years we have known that you are twice as likely to have osteoarthritis if your parents have the disease, yet we haven’t known why.

“Until we understand the cause of this complex disease, we cannot hope to find a cure. This is a major breakthrough in our understanding of osteoarthritis which we hope will help us to unlock the genetic basis of the disease.”

Further work is now needed to pinpoint the actual DNA changes within the genetic regions to establish exactly how these changes lead to osteoarthritis.

Professor Loughlin said that they were not yet able to use their discoveries as a tool to predict who was more or less likely to develop the disease, or to predict the degree of osteoarthritis severity, based on the genes they have inherited. Far more genes are involved in causing disease susceptibility than was previously thought, and there are still many left to find.

Professor Loughlin added: “However, what we are able to do is to use our genetic discoveries to identify key biological pathways that can now be exploited to develop new treatments.”

About arcOGEN:
The arcOGEN project was a major collaboration bringing together 16 academic investigators from across the UK, and at a cost of £2.2million was the biggest-ever single grant funded by Arthritis Research UK. The investigators were Professor Loughlin, Professor Andrew McCaskie and Dr Fraser Birrell from Newcastle University, Professor Nigel Arden, Professor Andrew Carr and Dr Kay Chapman from the University of Oxford, Professor Tim Spector and Dr Anna Valdes from King’s College London, Professor Michael Doherty from the University of Nottingham, Professor Mark Wilkinson from the University of Sheffield, Professor Bill Ollier and Professor Gillian Wallis from the University of Manchester, Professor Ashok Rai from the University of Worcester, Professor Stuart Ralston from the University of Edinburgh, and Dr Panos Deloukas and Dr Ele Zeggini from the Wellcome Trust Sanger Institute.

Read a Q&A about arcOGEN.

Can the arcOGEN study help future generations?

Terry Lawrence and her family

In a special feature, Arthritis Today highlights the first of three important new studies which could have a major impact on osteoarthritis treatment – now and in the future.

arcOGEN Q & A

Read the answers to your questions about arcOGEN and what it means for you.

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Arthritis Research UK fund research into the cause, treatment and cure of arthritis. You can support Arthritis Research UK by volunteering, donating or visiting our shops.