Causal effects between negative moods and cardiovascular diseases: a Mendelian randomization study

Abstract Background. Previous observational studies have found that negative moods are associated with cardiovascular diseases (CVDs). However, their causal association remains unclear. We aim to evaluate the causal associations of genetically determined negative moods with CVDs including coronary artery disease (CAD), myocardial infarction (MI), stroke, and subtypes of stroke using Mendelian randomization study. Methods. Summary statistics for negative moods were extracted from the UK Biobank and a large genome-wide association study including 366,726 subjects. Six negative moods, tiredness, depressed mood, tenseness, unenthusiasm, anxiety, and anger, were included. Genetic associations with CVDs were extracted from the CardiogramplusC4D consortium and MEGASTROKE consortium: CAD (n = 184,305), MI (n = 171,875), stroke (n = 446,696), and subtypes of stroke. Causal effects were inferred between related traits by univariable, reverse and multivariable Mendelian randomization (MR) method. Results. Univariable MR analyses found that tiredness was genetically correlated with CAD (OR 1.91; 95% CI 1.23–2.97; P = 0.004) and MI (OR 2.12; 95% CI 1.29–3.47; P = 0.003). Besides, we found that the genetic liability to depressed mood was associated with higher risks of CAD (OR 2.97; 95%CI: 1.25–7.09; P = 0.014) and MI (OR 2.81; 95%CI: 1.06–7.42; P = 0.037). No causal relationship between negative moods and stroke was found. Bidirectional MR analysis failed to find any significant causal effect of CVDs on the risk of negative moods. Multivariable MR analyses revealed compelling evidence of tiredness on the risk of CAD and MI. However, after adjusting for other cardiovascular risk traits, the causal relationship between depressed mood and CVDs disappeared. Conclusions. This MR study found that genetic predisposition to tiredness may have a causal effect on the risk of CAD and MI. Early diagnosis and prevention of tiredness may be helpful in the management of CAD and MI.