Exploring the causal association between congenital heart disease and stroke based on two-sample Mendelian...

Area of Science:

• Cardiovascular Genetics
• Epidemiology
• Medical Research

Background:

• Understanding the pathological mechanisms and genetic factors in congenital heart disease (CHD) is crucial for survivors.
• Survivors of CHD are at increased risk for secondary cardiovascular diseases.
• Genetic predisposition may link CHD to acquired cardiovascular conditions.

Purpose of the Study:

• To investigate potential causal links between CHD and acquired cardiovascular diseases.
• Utilize genetic data to explore associations between specific CHD types and cardiovascular outcomes.
• Identify genetic instruments for risk stratification in CHD patients.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design using genome-wide association study (GWAS) summary data.
• Analyzed data for CHD (congenital anomalies of great vessels, heart septal defect) and seven cardiovascular diseases.
• Applied inverse variance weighted (IVW), weighted median, and MR-Egger methods, with sensitivity analyses including MR-Egger, MR-PRESO, and Cochran's Q.

Main Results:

• Identified a potential association between congenital anomalies of great vessels and increased risk of atrial fibrillation (OR=1.07, P=0.004).
• Found associations between congenital anomalies of great vessels and higher risk of unspecified stroke (OR=1.07, P=0.008) and ischemic stroke (OR=1.07, P=0.02).
• Sensitivity analyses confirmed no significant horizontal pleiotropy or single-mutation-driven effects.

Conclusions:

• Congenital anomalies of great vessels may causally increase the risk of atrial fibrillation and stroke in CHD survivors.
• Genetic factors identified could aid in predicting higher risks for stroke and other cardiovascular diseases.
• Further research into genetic links can improve prevention and management strategies for CHD patients.