Largest Genome-Wide Association Study Uncovers New Drug Targets and Potential Therapies for Osteoarthritis

About one in five  American adults have osteoarthritis, the most common form of arthritis,  according to the Centers for Disease Control and Prevention. No treatment, however, exists to target the causes of the disease or to reverse or halt the damage the disease does to joints. Medications currently on the market only to help patients manage symptoms like joint pain, stiffness and mobility issues. In an effort to learn more about the genetic underpinnings of the condition –which is expected to afflict 1 billion people worldwide by 2050 – a team of international researchers conducted the largest genome-wide association study ever performed on osteoarthritis.

They conducted a meta-analysis of genetic databases involving nearly 2 million people including nearly half-million patients with osteoarthritis and 1.5 million controls. They found 962 genetic markers that were associated with the condition, including 513 new ones that were never reported in previous studies.  Results were published this week in the journal 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.

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.

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."