Researchers found hundreds of genes linked to osteoarthritis, opening doors to new and repurposed treatments. The findings may help personalize care and speed up drug development.
About one in five American adults has osteoarthritis, the most common form of arthritis, according to the Centers for Disease Control and Prevention. Currently, there is no treatment that targets the root causes of the disease or stops the joint damage it causes. Existing medications only help manage symptoms such as joint pain, stiffness, and reduced mobility.
To better understand the genetic factors behind osteoarthritis, which is projected to affect 1 billion people globally by 2050, an international team of researchers conducted the largest genome-wide association study on the condition to date.
The researchers performed a meta-analysis of genetic data from nearly 2 million individuals, including approximately 500,000 people with osteoarthritis and 1.5 million control subjects. They identified 962 genetic markers linked to the disease, 513 of which had not been previously reported. The findings were recently published in Nature.
“This is an exciting set of findings that have identified hundreds of potential new drug targets and opportunities for repurposing drugs already approved and on the market for other conditions,” said study co-author Marc C. Hochberg, MD, MBA, Professor Emeritus of Medicine at the University of Maryland School of Medicine. He has led studies focusing on the clinical epidemiology of osteoarthritis and other musculoskeletal disorders and also served as the Principal Investigator of the Baltimore Clinical Center for the Osteoarthritis Initiative and the Study of Osteoporotic Fractures.
New Drug Targets and Repurposing Opportunities
The research team for the new Nature study conducted the largest genome-wide association meta-analysis ever performed on osteoarthritis, providing potential new ways to understanding the biological processes leading to the development of this inflammatory disease.
By integrating diverse biomedical datasets, the researchers identified 700 genes with high confidence as being involved in osteoarthritis. Notably, 10 percent of these genes encode proteins that are already targeted by approved drugs. This could enable existing medications approved for other conditions to be repurposed as arthritis treatments.
“With 10 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 Eleftheria Zeggini, PhD, Director of the Institute of Translational Genomics at Helmholtz Munich and Professor of Translational Genomics at the Technical University of Munich.
Potential for Precision Medicine
Beyond identifying genetic targets with therapeutic potential, the study also provides valuable insights that could help tailor treatment strategies or potentially enable improved patient selection for clinical trials and precision 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.
The study, which included 87 percent of samples from those of European ancestry, was not statistically powered to identify novel signals in populations who were not of European descent.
“In the U.S., total costs attributed to osteoarthritis pain and disability average more than $486 billion every year, which is astonishing and points to the need to develop more effective treatments,” said Mark T. Gladwin, MD, who is the John Z. and Akiko K. Bowers Distinguished Professor and Dean of University of Maryland School of Medicine. “In developing new treatments, it is crucial to enhance wider participation in these genome-wide studies so that we can identify novel genetic associations across a broader spectrum of populations.”
Reference: “Translational genomics of osteoarthritis in 1,962,069 individuals” by 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, arcOGEN Consortium, ARGO Consortium, DBDS Genomic Consortium, Estonian Biobank Research Team, FinnGen, Genes & Health Research Team, HUNT All-In Pain, Million Veteran Program, Regeneron Genetics Center, 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 and Eleftheria Zeggini, 9 April 2025, Nature.
DOI: 10.1038/s41586-025-08771-z
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