Positive association and shared genetic structure between cardiovascular diseases and osteoarthritis: Insights from cross-sectional study and genome-wide pleiotropic analysis
Aug 2026· Therapeutic Advances in Musculoskeletal Disease· Vol 18· 0 citations· 56 references
Medicine
TL;DR
A positive association was observed between the prevalence of CVDs and OA, potentially explained by shared genetic factors, and Pathway assessment and multi-trait colocalization suggested that abnormal lipid metabolism may be a common cause of CVDs and OA.
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.
This study indicates a genetic correlation and common risk genes, linking adiposity-related traits to PE-related diseases, and offers novel insights into the biological mechanisms underlying this comorbidity.
Yuping Shan, Hong Hu, Chong Liu et al.· Journal of Obstetrics and Gy...· 0 citations
COPD and retinal vascular traits show evidence of shared genetic architecture involving vascular branching, density, and venous caliber, and support retinal vascular traits as candidate research phenotypes for investigating systemic microvascular involvement in COPD.
Yu-Li Chen, Yi-Bin Li, Yijiao Tang et al.· International Journal of COP...· 0 citations
Metabolic syndrome (MetS), characterized by a cluster of interrelated metabolic abnormalities including central obesity, elevated blood pressure, dysglycemia, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol (HDL-C), substantially increases type 2 diabetes and cardiovascular disease risk. Conventional genome-wide association studies (GWASs) analyze individual traits or a dichotomized MetS status, only partially capturing its heritability and potentially overlooking variants with shared (pleiotropic) effects across correlated traits. Here, we performed a multiple-trait GWAS using data from the Korean Genome and Epidemiology Study. Using the Korea Biobank Array (K-Chip), we analyzed a discovery cohort from the Ansan and Ansung studies (1490 cases and 3856 controls) and validated the findings in CAVAS (3620 cases and 4461 controls) and HEXA (15,257 cases and 41,807 controls) cohorts. We jointly modeled six MetS-related traits using the complementary multivariate frameworks Multiple Phenotype Association Tests and Genome-wide Efficient Mixed Model Association, alongside a baseline logistic regression. Whereas logistic regression detected 2 APOA5 variants (rs662799 and rs2075291), the multivariate analyses identified 79 significant single-nucleotide polymorphisms; all were replicated in the HEXA cohort. Functional annotation prioritized 27 high-risk variants mapping to 12 genes, whereas pathway analysis (DAVID) implicated eight Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways related to lipid metabolism. Our findings demonstrate that multivariate analysis substantially improves the identification of pleiotropic susceptibility loci for MetS in the Korean population and indicates candidate genes for early detection and management.
Dasom Kim, Jun-Ho Cha, Sungkyoung Choi· International Journal of Mol...· 0 citations
Evidence is provided for a shared, albeit modest, and genetic basis between EMS and IBD that is likely mediated through immune regulation, hormonal signaling, and tissue repair that is likely mediated through immune regulation, hormonal signaling, and tissue repair.
Xinyue Cui, Jian-Hong Wang, Jingjing Chen et al.· BioMed Research Internationa...· 0 citations
Objective This study used two-sample Mendelian Randomization to investigate the causal link between multiple biological aging indicators and vascular disease. Methods Summary genetic data was obtained from genome-wide association studies (GWAS) focusing on aging-related exposures and various vascular disease outcomes. The exposures included granulocyte proportions, PAI-1 (plasminogen activator inhibitor-1), telomere lengths, and the Frailty Index. The primary analysis employed the Inverse Variance Weighted (IVW) method to estimate causal relationships, supported by MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran’s Q test, MR-Egger regression, leave-one-out test, and the MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) test, were conducted to evaluate heterogeneity and pleiotropy. Results The analysis revealed distinct pathways after sensitivity adjustments. A higher genetically predicted Frailty Index was associated with an increased risk of abdominal aortic aneurysm (OR=2.5935, 95% CI: 1.3936–4.8268, P=0.0026, false discovery rate (FDR)=0.0475), atherosclerosis excluding cerebral and coronary sclerosis (OR=2.0262, 95% CI:1.5179–2.705, P=1.66×10-6, FDR=1×10-4), and arterial thromboembolic events (OR = 4.0306, 95% CI: 1.7133–9.4818, P = 0.0014, FDR = 0.0337). Conversely, longer telomere length demonstrated a strong, specific protective effect against abdominal aortic aneurysm (OR=0.5008, 95% CI:0.4111–0.6100, P=6.42×10-12, FDR=9.25×10-10), indicating that shorter telomere length is associated with an increased risk of AAA. Furthermore, a lower granulocyte proportion was causally linked to an increased risk of thoracic aortic aneurysm (OR=0.0181, 95% CI: 0.0014–0.2376, P=0.0023, FDR=0.0465). Conclusion This study identifies three genetic pathways linking biological aging to vascular disease, offering new molecular targets for its prevention and treatment.
Hao Yan, Shang Wei, Hui Hui et al.· Clinical and applied thrombo...· 0 citations
Understanding whether and how shared genetic factors contribute to the comorbidity between stress-related disorders (SRDs) and cardiovascular disease (CVD) is important for integrated prevention and treatment, but current evidence remains limited. To address this gap, we integrated Swedish national registers (n = 4,123,631), UK Biobank (n = 502,291), and genome-wide association study summary statistics to explore shared genetic liability between SRDs and six CVD subtypes and to nominate pleiotropic loci, genes, and enriched pathways. Familial coaggregation analyses showed that the SRDs-CVD association attenuated with decreasing genetic relatedness among relatives, supporting the existence of shared genetic influences. Polygenic risk scores for SRDs significantly predicted a higher risk of any CVD and all subtypes (odds ratios = 1.05-1.09), and all SRDs-CVD pairs showed positive genetic correlations (rg = 0.09-0.35), whereas Mendelian randomization (MR) analyses did not support strong causal effects in either direction. Genome-wide cross-trait analyses identified 17 putative pleiotropic loci, and consensus-based gene mapping prioritized 16 putative pleiotropic genes. Enrichment analyses indicated that pleiotropic signals were enriched in processes related to hemostasis and coagulation, circulatory system development, and telomere maintenance. In validation analyses focusing on post-traumatic stress disorder (PTSD), we observed a similar pattern of genetic overlap with CVD and replicated a subset of loci, genes, and pathways. These findings support a genetic comorbidity framework in which shared genetic liability, largely driven by pleiotropic loci, contributes to the co-occurrence of SRDs and CVD and highlight candidate genes and biological processes for future experimental studies.
C. Hou, Yu Zeng, Huazhen Yang et al.· Genomics, Proteomics & Bioin...· 0 citations
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