December 9, 2024

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Genetic links between osteoarthritis and cardiovascular disease reveal hidden common risks

Exploring shared genes in osteoarthritis and cardiovascular disease, researchers uncover genetic connections that could reshape prevention strategies for both conditions.

Study: Shared genetic factors between osteoarthritis and cardiovascular disease may underlie common etiology. Image Credit: Sergey Nivens / Shutterstock.com

A recent study published in the journal Nature Communications identifies shared genetic risk factors between osteoarthritis and cardiovascular disease, which may contribute to the etiology of both diseases. 

Cardiovascular disease and osteoarthritis

Osteoarthritis is one of the most prevalent musculoskeletal diseases worldwide and is associated with a wide range of health complications, including cardiovascular disease. Both osteoarthritis and cardiovascular disease may arise due to numerous environmental risk factors, including advanced age, smoking, physical inactivity, and obesity. In some patients, these two diseases co-occur, which could be due to these shared environmental risk factors or a shared genetic liability.

Although certain genetic risk factors significantly contribute to the etiologies of both osteoarthritis and cardiovascular disease, it remains unclear the extent to which these diseases share the same etiology in terms of genetic liability.

Important observations

In the current study, scientists explore whether co-occurrence of osteoarthritis and cardiovascular disease is due to shared genetic or environmental risk factors. To this end, data from twin studies were analyzed to explore shared genetic and environmental factors associated with osteoarthritis and cardiovascular disease.

A total of 59,970 twins in 29,985 twin pairs were included in the final analysis. Among the study participants, 7,363 had hand, hip, or knee joint osteoarthritis, and 13,685 had one form of severe cardiovascular disease, including cardiac arrhythmias, coronary heart disease, heart failure, and stroke.

Osteoarthritis and cardiovascular disease were identified as the most prevalent combined diagnoses. Concordance for these diagnoses was higher in monozygotic twins as compared to dizygotic twins.

The analysis of genetic and environmental factors revealed that a major part of the co-occurrence between osteoarthritis and cardiovascular disease can be explained by shared genetic factors that are independent of age, sex, educational level, body mass index (BMI), smoking status, and physical activity level.

A shared genetic liability contributed more to the co-occurrence of severe cardiovascular diseases with hip osteoarthritis than with knee osteoarthritis. The analysis identified unique environmental factors that contribute to the co-occurrence of knee osteoarthritis and severe cardiovascular diseases.

Among specific cardiovascular diseases present in the study participants, shared genetic factors contributed more to the co-occurrence of osteoarthritis with cardiac arrhythmia, coronary heart disease, or stroke. Comparatively, unique environmental factors had a larger role in the co-occurrence of osteoarthritis and heart failure; however, this observation is unclear due to the scarcity of cases. 

Study significance

Generic risk factors shared by osteoarthritis and cardiovascular diseases may contribute to the etiology of both diseases, independent of the influence of common environmental risk factors. This finding challenges existing beliefs that osteoarthritis is a predominant risk factor for cardiovascular diseases.

These observations can explain, at least in part, the findings from a previous meta-analysis reporting a 24-69% increased risk of cardiovascular disease in osteoarthritis patients as compared to the general population.

The unique environmental factors influencing the co-occurrence of these diseases indicate the existence of an opposite effect on the two outcomes of interest, similar to what happens in sports performances, where high-level participation increases the risk of injury and subsequent osteoarthritis but reduces the risk of cardiovascular diseases.

The observed genetic overlap between osteoarthritis and cardiovascular disease highlights the need for re-evaluating current diagnostic boundaries between these diseases. The scientists also highlight the possibility of a distinct osteoarthritis/cardiovascular disease phenotype, which needs further investigation. Future studies should also identify specific genes or genetic markers that might explain the shared heritability of these diseases and investigate the role of typical lifestyle factors in modifying genetic influence.

Parental osteoarthritis or cardiovascular disease increases the risk of developing these diseases in offspring, thus emphasizing the importance for physicians to examine the family history of these diseases in their patients. Therefore, in addition to providing new insights into disease etiology, the study findings may facilitate the early detection or prevention of comorbid disease and the development of personalized medicine with the aim of preventing severe disease and disability.

A significant strength of this study is the inclusion of a large, population-based twin sample with limited selection bias and a high degree of generalizability. The study used a similar twin modeling strategy across a range of osteoarthritis and cardiovascular diseases, which may serve as a basis for estimating more complex genetic and environmental mechanisms.

Journal reference:

  • Magnusson, K., Turkiewicz, A., Dell’Isola, A., & Englund, M. (2024). Shared genetic factors between osteoarthritis and cardiovascular disease may underlie common etiology. Nature Communications. doi:10.1038/s41467-024-53812-2

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