Team Head
Michelle Lupton
The world’s largest study of the genetics of osteoarthritis has identified more than 500 previously unknown genetic links to the disease, and hundreds of potential new drug targets that could fast track the development of more effective treatments.
The findings from an international research team led by Helmholtz Munich in Germany, and involving QIMR Berghofer scientists, have been published in Nature.
Osteoarthritis is the most common form of arthritis. The complex disease is caused by environmental and genetic risk factors that lead to the breakdown of cartilage at the end of joints, often in the knees, hands and hips.
Almost 600 million people are affected globally, including more than two million Australians. The number of patients is predicted to increase to one billion by 2050, making osteoarthritis one of the fastest growing health conditions in the world.
QIMR Berghofer Associate Professor Michelle Lupton said the disease is a leading cause of pain and disability, and new treatments are urgently needed.
“This study is a significant advance in our understanding of osteoarthritis. It could help pave the way for treatments that actually modify the disease, not just treat symptoms such as pain.
“We are very proud to have played a role in this global research by contributing data from our own studies in Australia,” A/Prof Lupton said.
The researchers uncovered 513 new genetic associations linked to osteoarthritis, bringing the total number of known genetic links to 962.
Further analysis found 700 ‘effector’ genes, which are genes that are very likely to be involved in the development of the disease. The study identified more than 470 approved drugs that could target proteins expressed by 69 of these genes. This opens up opportunities to repurpose existing drugs which could accelerate the development of new treatments.
The research also pinpointed eight biological processes involved in osteoarthritis development, providing further targets for therapeutic interventions. These processes include the circadian rhythm which is the body’s internal clock, and glial cell functions which support the nervous system.
The new insights into the genetic architecture of osteoarthritis could lead to more personalised treatment strategies, and help improve the design of clinical trials.
The genome-wide association (GWAS) study is the largest ever performed for osteoarthritis. It analysed data from genetic samples donated by nearly two million people globally, including nearly 490,000 people diagnosed with the disease.
The datasets included thousands of Australians who participated in the following QIMR Berghofer-led studies: the Over 50’s, and Osteoarthritis Studies; Prospective Imaging Study of Ageing (PISA).Australian Genetics of Bipolar Disorder Study (GBP), and the Australian Genetics of Depression Study (AGDS). All were funded by the National Health and Medical Research Council (NHMRC).
A/Prof Lupton said: “Very large sample sizes are needed to more accurately uncover genetic links to disease. We are very grateful to everyone who took part in our studies. Sharing this data with our international collaborators has enabled the discovery of genetic and biological findings that could transform osteoarthritis care and improve quality of life for millions of people.”
The paper is available at this link https://www.nature.com/articles/s41586-025-08771-z in Nature with DOI 10.1038/s41586-025-08771-z.