Causal effects of risky behaviours on heart failure: a two-sample Mendelian randomisation study

Aims/Background Previous studies have indicated correlations between various risky behaviours, increased risk tolerance, and the likelihood of heart failure. However, the causative nature of these correlations remains to be established. Therefore, our research aims to explore the causality between phenotypes of risky behaviour and the incidence of heart failure. Methods To assess causality, a two-sample Mendelian randomisation analysis was employed. Genetic variants of risky behaviours and risk tolerance (n=251,151-939,908) were sourced from existing genome-wide association summary statistics. For heart failure, genetic links were derived from a separate genome-wide association summary statistics dataset involving 977,323 individuals, comprising 47,309 heart failure cases and 930,014 controls. The primary method for this analysis was the inverse variance weighted technique. Results Mendelian randomisation analysis indicated a positive association between the number of offspring an individual has and the likelihood of heart failure (odds ratio, 1.841; 95% confidence interval, 1.528-2.217, p=1.26 × 10^-10). Additionally, a modest statistically significant link was found between overall risk tolerance and heart failure (odds ratio, 1.249; 95% confidence interval, 1.003-1.556, p=0.047). Conversely, a genetic predisposition towards frequent automobile speeding showed a protective effect against heart failure (odds ratio, 0.732; 95% confidence interval, 0.545-0.982, p=0.037). Conclusion This Mendelian randomisation study confirmed genetically that risky behaviours are causally linked to the likelihood of heart failure. This finding may offer fresh perspectives on the pathogenic mechanisms underlying the progression of heart failure.