Ankylosing spondylitis and cardiovascular disease: A two-sample Mendelian randomization analysis

Area of Science:

• Genetics
• Cardiology
• Rheumatology

Background:

• Epidemiological studies suggest a link between ankylosing spondylitis (AS) and cardiovascular disease (CVD).
• The genetic basis for the association between AS and CVD risk remains unclear.

Purpose of the Study:

• To investigate the potential causal relationship between genetically determined ankylosing spondylitis and various cardiovascular disease outcomes.
• To analyze the impact of AS genetic susceptibility on the risk of developing specific CVDs.

Main Methods:

• A two-sample Mendelian randomization analysis was performed using European genome-wide association study data for AS and CVD.
• Single nucleotide polymorphisms associated with AS genetic susceptibility were used as instrumental variables.
• Inverse variance weighted methods were employed to assess causal effects, with replication and sensitivity analyses conducted.

Main Results:

• Genetic susceptibility to AS was significantly associated with an increased risk of heart failure (OR=1.0128, P=0.0058), hypertension (OR=1.0143, P=0.0073), and ischemic stroke (OR=1.0151, P=0.0036) in the European population.
• No significant association was found between AS genetic susceptibility and coronary heart disease, cardiomyopathy, valvular heart disease, or atrial fibrillation (all P > 0.05).
• Sensitivity analyses confirmed the reliability of the findings.

Conclusions:

• Genetically determined ankylosing spondylitis is associated with a higher risk of heart failure, hypertension, and ischemic stroke.
• These findings highlight a potential genetic link between AS and specific cardiovascular conditions.
• Further research is warranted to elucidate the underlying biological mechanisms connecting AS genetics to CVD risk.