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

Abstract

Background: Research into common pathological mechanisms and genetic factors is essential for better understanding, prevention and management of cardiovascular disease in congenital heart disease (CHD) survivors. This study aims to explore the possible causal associations between CHD and acquired cardiovascular diseases with the help of genetic instruments.

Methods: This study utilized summary data from genome-wide association studies (GWASs) of CHD (including congenital anomalies of great vessels and heart septal defect) and seven different cardiovascular diseases, employing a two-sample Mendelian randomization (MR) design. Analysis was conducted using the inverse variance weighted method (IVW), weighted median, weighted mode, and MR-Egger regression methods. Sensitivity analysis included MR-Egger, MR-PRESO, Cochran's Q, and leave-one-out.

Results: In this study, 15 instrumental variables related to CHD were selected [F-statistic =23.55 (21.27, 28.84)]. The IVW MR analysis revealed potential association between genetically predicted congenital anomalies of great vessels and higher risk of atrial fibrillation [odds ratio (OR) =1.07, 95% confidence interval (CI): 1.02-1.12, P=0.004], unspecified stroke (OR =1.07, 95% CI: 1.02-1.12, P=0.008) and ischemic stroke (OR =1.07, 95% CI: 1.01-1.14, P=0.02). No significant associations were observed between other factors. The MR-Egger regression results indicated that these analyses were not affected by horizontal pleiotropy. Leave-one-out analysis showed that the causal effects were not driven by any single mutation.

Conclusions: This study found a potential causal association between exposure to congenital anomalies of great vessels and higher risk of atrial fibrillation, stroke and ischemic stroke. Discussed genetic factors might potentially help to identify a higher risk of stroke and other cardiovascular diseases.