Genetic and phenotypic relationships between coronary atherosclerotic heart disease and electrocardiographic traits

Observational studies have revealed that Coronary Atherosclerotic Heart Disease (CAHD) is associated with abnormal electrocardiogram (ECG) traits. However, it remains unclear whether there are genetic correlations between ECG and CAHD. Here, we explored genetic correlations and putative causal relationships between CAHD and ECG by performing Mendelian randomization (MR) and Polygenic risk score (PRS) analyses on the summary statistics from a large-scale genome-wide association study (GWAS) for CAHD (FinnGen: Ncase 23363, Ncontrol 187840) and ECG traits (UK Biobank: Ncase=1137, Ncontrol=40823). Results showed a causal genetic relationship between CAHD and six ECG traits in the lead V6. These ECG traits combining with age and gender have predicted CAHD risk with an AUC of 0.76. Further summary data-based Mendelian randomization (SMR) analysis identified 11 risk genes associated with the causality between CAHD and ECG. Thus, the revealed putative causal effects of CAHD on ECG traits provide genetic evidence to support the importance of monitoring CAHD risk through the ECG.