Effect of worry, depression, and sensitivity to environmental stress owing to neurotic personality on risk of cardiovascular disease: A Mendelian randomization study

OBJECTIVE: This study investigated the putative causal link between neuroticism (using three genetically distinct subclusters namely depressed affect, worry, and sensitivity to environmental stress and adversity [SESA]) and cardiovascular disease (CVD). METHOD: A two-sample bi-directional Mendelian randomization (MR) approach was used. Genetic instruments were extracted from publically available GWAS summary statistics. RESULTS: In forward MR analyses with neuroticism subclusters as exposures, no causal associations between worry or SESA cluster and any of the CVD traits were observed (p > .05 for all). However, a higher risk of having heart failure (odds ratio (95% confidence interval):1.32(1.12 to 1.56); p = .0011) and myocardial infarction (1.47[1.18 to 1.83]; p = 6.3 × 10-4) associated with depressed affect cluster was observed. In reverse MR analyses with CVD traits as exposures, no significant associations were observed (p > .05 for all). CONCLUSIONS: Individuals with high neuroticism who are more susceptible to depressive symptoms are at higher risk for developing heart failure and myocardial infarction and should be more carefully evaluated for CVD risk in clinical settings. These individuals can potentially benefit from interventions aimed at reducing depressive symptoms to decrease CVD risk. There is no evidence to suggest that being sensitive to environmental stressors or being more worried can increase the risk for CVD.