PhD defence Y. (Yahong) Wu

Below is a brief summary of the dissertation:

Osteoarthritis is one of the most common chronic diseases worldwide and a major cause of pain and disability in older adults. Despite its high prevalence, the factors that lead to its development are not fully understood. This thesis combines epidemiological and genetic approaches to investigate risk factors and biological mechanisms underlying osteoarthritis.

First, we studied the relationship between physical activity, lower-limb muscle mass, and the development of knee osteoarthritis. Weight-bearing activities, such as walking and jogging, were associated with an increased risk of knee osteoarthritis only in individuals with relatively low muscle mass, suggesting that stronger muscles may protect the joints.

Second, we examined chondrocalcinosis, a condition characterized by calcium crystal deposits in cartilage. We showed that chondrocalcinosis precedes and increases the risk of developing knee osteoarthritis, indicating that it may be a contributing cause rather than simply a consequence of joint damage.

Third, we investigated the genetic basis of chondrocalcinosis and identified genes involved in crystal formation and thyroid-related pathways.

Finally, using genetic data from nearly two million individuals, we identified 66 new genetic signals associated with osteoarthritis and showed that some genetic factors are shared across joints, while others have different effects depending on the joint.

Together, these findings improve our understanding of osteoarthritis and may contribute to better prevention and more personalized treatment.