Osteoarthritis: Largest genome-wide association study uncovers drug targets and therapy opportunities
- Date:
- April 9, 2025
- Source:
- Helmholtz Munich
- Summary:
- 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 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.
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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.
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.
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)
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Materials provided by Helmholtz Munich. Note: Content may be edited for style and length.
Journal Reference:
- Konstantinos Hatzikotoulas, Lorraine Southam, Lilja Stefansdottir, Cindy G. Boer, Merry-Lynn McDonald, J. Patrick Pett, Young-Chan Park, Margo Tuerlings, Rick Mulders, Andrei Barysenka, Ana Luiza Arruda, Vinicius Tragante, Alison Rocco, Norbert Bittner, Shibo Chen, Susanne Horn, Vinodh Srinivasasainagendra, Ken To, Georgia Katsoula, Peter Kreitmaier, Amabel M. M. Tenghe, Arthur Gilly, Liubov Arbeeva, Lane G. Chen, Agathe M. de Pins, Daniel Dochtermann, Cecilie Henkel, Jonas Höijer, Shuji Ito, Penelope A. Lind, Bitota Lukusa-Sawalena, Aye Ko Ko Minn, Marina Mola-Caminal, Akira Narita, Chelsea Nguyen, Ene Reimann, Micah D. Silberstein, Anne-Heidi Skogholt, Hemant K. Tiwari, Michelle S. Yau, Ming Yue, Wei Zhao, Jin J. Zhou, George Alexiadis, Karina Banasik, Søren Brunak, Archie Campbell, Jackson T. S. Cheung, Joseph Dowsett, Tariq Faquih, Jessica D. Faul, Lijiang Fei, Anne Marie Fenstad, Takamitsu Funayama, Maiken E. Gabrielsen, Chinatsu Gocho, Kirill Gromov, Thomas Hansen, Georgi Hudjashov, Thorvaldur Ingvarsson, Jessica S. Johnson, Helgi Jonsson, Saori Kakehi, Juha Karjalainen, Elisa Kasbohm, Susanna Lemmelä, Kuang Lin, Xiaoxi Liu, Marieke Loef, Massimo Mangino, Daniel McCartney, Iona Y. Millwood, Joshua Richman, Mary B. Roberts, Kathleen A. Ryan, Dino Samartzis, Manu Shivakumar, Søren T. Skou, Sachiyo Sugimoto, Ken Suzuki, Hiroshi Takuwa, Maris Teder-Laving, Laurent Thomas, Kohei Tomizuka, Constance Turman, Stefan Weiss, Tian T. Wu, Eleni Zengini, Yanfei Zhang, George Babis, David A. van Heel, Bendik Winsvold, Maiken Gabrielsen, Manuel Allen Revez Ferreira, George Babis, Aris Baras, Tyler Barker, David J. Carey, Kathryn S. E. Cheah, Zhengming Chen, Jason Pui-Yin Cheung, Mark Daly, Renée de Mutsert, Charles B. Eaton, Christian Erikstrup, Ove Nord Furnes, Yvonne M. Golightly, Daniel F. Gudbjartsson, Nils P. Hailer, Caroline Hayward, Marc C. Hochberg, Georg Homuth, Laura M. Huckins, Kristian Hveem, Shiro Ikegawa, Muneaki Ishijima, Minoru Isomura, Marcus Jones, Jae H. Kang, Sharon L. R. Kardia, Margreet Kloppenburg, Peter Kraft, Nobuyuki Kumahashi, Suguru Kuwata, Ming Ta Michael Lee, Phil H. Lee, Robin Lerner, Liming Li, Steve A. Lietman, Luca Lotta, Michelle K. Lupton, Reedik Mägi, Nicholas G. Martin, Timothy E. McAlindon, Sarah E. Medland, Karl Michaëlsson, Braxton D. Mitchell, Dennis O. Mook-Kanamori, Andrew P. Morris, Toru Nabika, Fuji Nagami, Amanda E. Nelson, Sisse Rye Ostrowski, Aarno Palotie, Ole Birger Pedersen, Frits R. Rosendaal, Mika Sakurai-Yageta, Carsten Oliver Schmidt, Pak Chung Sham, Jasvinder A. Singh, Diane T. Smelser, Jennifer A. Smith, You-qiang Song, Erik Sørensen, Gen Tamiya, Yoshifumi Tamura, Chikashi Terao, Gudmar Thorleifsson, Anders Troelsen, Aspasia Tsezou, Yuji Uchio, A. G. Uitterlinden, Henrik Ullum, Ana M. Valdes, David A. van Heel, Robin G. Walters, David R. Weir, J. Mark Wilkinson, Bendik S. Winsvold, Masayuki Yamamoto, John-Anker Zwart, Kari Stefansson, Ingrid Meulenbelt, Sarah A. Teichmann, Joyce B. J. van Meurs, Unnur Styrkarsdottir, Eleftheria Zeggini. Translational genomics of osteoarthritis in 1,962,069 individuals. Nature, 2025; DOI: 10.1038/s41586-025-08771-z
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