Positive association and shared genetic structure between cardiovascular diseases and osteoarthritis: Insights from cross-sectional study and genome-wide pleiotropic analysis.

Abstract

Background: Osteoarthritis (OA) and cardiovascular diseases (CVDs) are leading global causes of disability. While evidence indicates a significant association in their prevalence, the underlying biological mechanisms driving this comorbidity remain unclear.

Objectives: This study seeks to elucidate the epidemiological association between OA and common CVDs, and investigate whether shared genetic architecture underlies their comorbidity.

Design: cross-sectional study and genome-wide pleiotropic analysis.

Methods: Among 21,019 participants, multivariable logistic regression was used to examine the associations between OA and five CVDs (angina pectoris, coronary artery disease, myocardial infarction, heart failure, and stroke). Genetic correlations were then estimated using large-scale GWAS summary data of European ancestry, with the OA GWAS specifically focusing on knee and hip. Subsequent pleiotropy and multi-trait colocalization analyses were performed to identify shared loci, genes, and biological mechanisms.

Results: A positive association was observed between the prevalence of CVDs and OA, potentially explained by shared genetic factors. The genetic correlations (rg) and P values were: AP-OA (rg = 0.2229, p < 0.001), CAD-OA (rg = 0.1530, p < 0.001), MI-OA (rg = 0.1685, p < 0.001), HF-OA (rg = 0.3094, p < 0.001), and stroke-OA (rg = 0.1605, p < 0.001), indicating a robust and consistent shared genetic architecture between OA and these cardiovascular conditions. A total of 80 pleiotropic loci were identified, with 20 showing significant colocalization. Gene-level analysis revealed 84 distinct pleiotropic genes, including APOE, SMG6, UQCC1, and FES. Tissue enrichment analysis highlighted the role of pleiotropic mechanisms in central and peripheral blood vessels. Pathway assessment and multi-trait colocalization suggested that abnormal lipid metabolism may be a common cause of CVDs and OA.

Conclusion: Our study revealed a positive association and a shared genetic connection between CVDs and OA, and illuminated the potential mechanisms that could be involved.