Genetic risk factors and causal associations with sudden cardiac arrest: A Mendelian randomization study

Sudden cardiac arrest (SCA) is a major cause of mortality, with complex etiology involving multiple genetic and environmental factors. In this study, we aimed to identify genetic risk factors for SCA and evaluate their causal associations using Mendelian randomization (MR) analysis. We retrieved summarized genome-wide association study data for various exposures and the SCA outcome from public databases. Four MR methods, including inverse variance weighted (IVW), Egger, weighted median, and weighted mode, were applied to estimate causal effects. All MR methods revealed significant positive causal associations with SCA from diastolic blood pressure (IVW: b = 0.09, P = 5 × 10-18), systolic blood pressure (IVW: b = 0.06, P = 5 × 10-25), and total cholesterol levels (IVW: b = 0.28, P = 4 × 10-3). No consistent causal link was found for heart rate, body mass index, type 2 diabetes, and certain cardiac electrophysiological factors (P values for all 4 MR methods were not consistently below the significance level of .05). These findings provide insights into the genetic architecture of SCA and highlight potential targets for risk stratification and preventive strategies.