Osteoarthritis and cardiovascular disease: A Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Cardiology

Background:

• Osteoarthritis (OA) and cardiovascular disease (CVD) are prevalent conditions with complex etiologies.
• Understanding potential causal links between OA subtypes and CVD is crucial for public health.
• Mendelian randomization (MR) offers a robust method to investigate genetic predispositions and causal inference.

Purpose of the Study:

• To investigate the potential causal relationships between hip osteoarthritis (HOA) and knee osteoarthritis (KOA) and cardiovascular diseases (CVD), including coronary heart disease (CHD), heart failure (HF), and stroke.
• To utilize genetic variants as instrumental variables for OA phenotypes to infer causality.
• To explore potential reverse causality from CVD to OA.

Main Methods:

• A two-sample Mendelian randomization study design was employed.
• Single nucleotide polymorphisms (SNPs) associated with HOA and KOA from genome-wide association studies (GWAS) in European ancestry populations served as instrumental variables.
• Inverse variance weighting (IVW) and other MR methods were used to estimate causal effects, with heterogeneity and sensitivity analyses performed.

Main Results:

• Hip osteoarthritis (HOA) showed a significant causal effect on the incidence of heart failure (HF) (OR: 1.0675, P=0.0066) and stroke (OR: 1.1368, P=9.9488e-06).
• Coronary heart disease (CHD) demonstrated a significant causal effect on knee osteoarthritis (KOA) (OR: 0.9011, P=0.0018).
• No significant causal associations were found for other tested relationships.

Conclusions:

• The study suggests potential causal links between HOA and increased risks of HF and stroke.
• Findings indicate a significant causal relationship between CHD and KOA risk.
• These results may inform novel therapeutic strategies for managing OA and CVD concurrently.