Osteoarthritis study uncovers new genetic links, drug targets

Researchers have conducted what is claimed to be the world’s largest study of the genetics of osteoarthritis, identifying more than 500 previously unknown genetic links to the disease as well as hundreds of potential new drug targets that could fast-track the development of more effective treatments. Their work has been published in the journal Nature.

Osteoarthritis 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. It is the leading cause of disability and chronic pain worldwide, affecting an estimated 595 million people — with projections that this number will rise to one billion by 2050. Yet despite its profound impact on individuals and societies, no disease-modifying treatments are currently available.

Now, an international team of researchers led by Helmholtz Munich has made new discoveries by analysing genetic samples donated by nearly two million people globally, including nearly 490,000 people diagnosed with the disease. Their genome-wide association study (GWAS) uncovered over 900 genetic associations, more than 500 of which had never been reported before — providing fresh insights into the genetic landscape of the disease.

By integrating diverse biomedical datasets, the researchers identified 700 genes with high confidence as being involved in osteoarthritis. Notably, 10% of these genes encode proteins that are already targeted by approved drugs, opening the door to drug repurposing opportunities that could accelerate treatment development.

“With 10% of our genetic targets already linked to approved drugs, we are now one step closer to accelerating the development of effective treatments for osteoarthritis,” said study leader Eleftheria Zeggini, Director of the Institute of Translational Genomics at Helmholtz Munich and Professor of Translational Genomics at the Technical University of Munich.

Beyond identifying genetic targets with therapeutic potential, the study also provides valuable insights that could help tailor treatment strategies. As explained by co-first author Dr Konstantinos Hatzikotoulas, from Helmholtz Munich, “Genetic variants associated with osteoarthritis risk are widespread across osteoarthritis patients. Our newly gained knowledge about them can enable improved patient selection for clinical trials and personalised medicine approaches.”

In addition to these genetic insights, the scientists identified eight key biological processes crucial to osteoarthritis development, including the circadian rhythm (the body’s internal clock) and glial cell functions, which support the nervous system. According to Hatzikotoulas, “Our discovery suggests that targeted interventions regulating one or more of these eight processes could play another significant role in slowing or even halting disease progression.”

“What we found in the largest osteoarthritis GWAS study not only advances our understanding of the disease but also lays the groundwork for developing more effective and personalised therapies that could transform osteoarthritis care,” Zeggini concluded.

Image credit: iStock.com/Vladyslav Severyn