01:31am Monday 14 October 2019

Major new study finds clues to the genetic causes of osteoarthritis

Publishing their findings in The Lancet today, 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 genes. 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 about 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 pain killers 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 Bill Ollier, from the University of Manchester’s Centre for Integrated Medical Research (CIGMR), said: “Osteoarthritis is one the most common conditions affecting adults and is responsible for causing much pain and suffering for a large proportion of the population. Unfortunately, this is becoming a larger health problem as we live longer. We are only now just beginning to identify the genetic and lifestyle factors involved in OA and work out how they interact to allow the disease to develop. Only by doing this will we be able to develop treatments to tackle the disease at an early stage and avoid surgical replacements of joints. This landmark study, supported by the Alzheimer’s Research UK, has brought together the major research groups working on OA in collaboration, rather than being in competition. This important study opens up a number of exciting new avenues for tackling this common condition.”

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.

Gillian Wallis, Professor of Genetics in Manchester’s Wellcome Trust Centre for Cell-Matrix Research, said: “It is very exciting that many of the chromosomal regions associated with osteoarthritis contain genes that are involved in the development, production and maintenance of healthy cartilage. This makes sense because cartilage is one of the tissues of the joint that is degraded by the osteoarthritic disease process. Knowing which genes contribute to osteoarthritis susceptibility provides a firm starting point for research into the causes of this complex disease which may identify new targets for drug development.”

Principal 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.”

Medical director of Arthritis Research UK Professor Alan Silman added: “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.

He 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.”


Notes for editors

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. For more information about the arcOGEN project go to www.arthritisresearchuk.org

About osteoarthritis:Osteoarthritis is the most common form of arthritis, affecting around 40 per cent of people over the age of 70. It is a complex disease of the musculoskeletal system with both genetic and environmental risk factors.

Osteoarthritis is characterised by cartilage degeneration in the joints that can cause pain, stiffness and swelling. It is one of the leading causes of chronic disability and impaired quality of life in the developed world.

Osteoarthritis represents a substantial public health burden in the UK and is the primary cause for total joint replacement (TJR) surgery (accounting for 80 per cent of TJR). Prevalence is increasing, in keeping with epidemiologically established risk factors in the population, i.e. age and obesity.

Heritability studies in twins, sibling-pairs and families have estimated that genetic factors account for approximately 50 per cent of the risk of developing osteoarthritis in the hip or knee, although precise estimates vary depending on sex, affected site, and severity of disease.

About Arthritis Research UK: Arthritis Research UK is the leading authority on arthritis in the UK, conducting scientific and medical research into all types of arthritis and musculoskeletal conditions. It is the UK’s fourth largest medical research charity and the only charity solely committed to funding research into the cause, treatment and cure of arthritis. For more information please visit: www.arthritisresearchuk.org

For further information contact:

Aeron Haworth
Media Relations
Faculty of Medical and Human Sciences
The University of Manchester

Tel: 0161 275 8383
Mob: 07717 881563
Email: aeron.haworth@manchester.ac.uk

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