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Osteoarthritis is the leading cause of disability and chronic pain worldwide, affecting an estimated 595 million people globally. Projections suggest that this number will rise to 1 billion by 2050. 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 studying the genetics of osteoarthritis in nearly 2 million individuals, uncovering hundreds of potential new drug targets and opportunities for repurposing existing treatments.
Ten Percent of Genetic Targets Linked to Approved Drugs
The research team conducted the largest genome-wide association study (GWAS) ever performed on osteoarthritis, uncovering over 900 genetic associations. More than 500 of these associations 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, ten percent 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 ten percent of our genetic targets already linked to approved drugs, we are now one step closer to accelerating the development of effective treatments for osteoarthritis," explains study leader Prof. Eleftheria Zeggini, Director of the Institute of Translational Genomics at Helmholtz Munich and Professor of Translational Genomics at the Technical University of Munich.
Personalizing Osteoarthritis Treatments
Beyond identifying genetic targets with therapeutic potential, the study also provides valuable insights that could help tailor treatment strategies. “Genetic variants associated with osteoarthritis risk are widespread across osteoarthritis patients,” says co-first author Dr. Konstantinos Hatzikotoulas. “Our newly gained knowledge about them can enable improved patient selection for clinical trials and personalized medicine approaches.” In addition to these genetic insights, the scientists identified eight key biological processes crucial to osteoarthritis development, including the circadian clock and glial cell functions. “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,” Hatzikotoulas adds.
“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 personalized therapies that could transform osteoarthritis care”, says Eleftheria Zeggini.
About the Researchers
Dr. Konstantinos Hatzikotoulas, Researcher at the Institute of Translational Genomics at Helmholtz Munich
Prof. Eleftheria Zeggini, Director of the Institute of Translational Genomics at Helmholtz Munich and Liesel Beckman Distinguished Professor of Translational Genomics at the Technical University of Munich (TUM)
About Helmholtz Munich
Helmholtz Munich is a leading biomedical research center. Its mission is to develop breakthrough solutions for better health in a rapidly changing world. Interdisciplinary research teams focus on environmentally triggered diseases, especially the therapy and prevention of diabetes, obesity, allergies, and chronic lung diseases. With the power of artificial intelligence and bioengineering, researchers accelerate the translation to patients. Helmholtz Munich has around 2,500 employees and is headquartered in Munich/Neuherberg. It is a member of the Helmholtz Association, with more than 43,000 employees and 18 research centers the largest scientific organization in Germany. More about Helmholtz Munich (Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH): www.helmholtz-munich.de/en
Prof. Eleftheria Zeggini
E-Mail: eleftheria.zeggini@helmholtz-munich.de
Hatzikotoulas, Southam, Stefansdottir, Boer, McDonald et al., 2025: Translational genomics of osteoarthritis in 1,962,069 individuals. Nature. DOI: 10.1038/s41586-025-08771-z
https://www.nature.com/articles/s41586-025-08771-z
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