Role of lifestyle factors in mediating the effect of mood swings on cardiovascular diseases: A mediation Mendelian randomization study

It has been found that individuals with psychiatric illnesses are predisposed to an elevated risk of cardiovascular diseases (CVDs). Mood swing is a clinically relevant characteristic linked to psychiatric disorders. This study examined the possible relationship between genetically predicted mood swings and CVDs risk. In this mediation Mendelian randomization (MR) study, we compiled data from genome-wide association studies examining mood swings (n = 451,619) and 5 CVDs among Europeans, including coronary artery disease (CAD) (n = 547,261), major coronary heart disease events (MCEs) (n = 361,194), all-cause heart failure (AHF) (n = 218,208), atrial fibrillation (n = 1030,836), and stroke (n = 446,696). The inverse variance weighting method was considered the primary assessment approach in MR analysis, and several sensitivity analyses were performed to evaluate the reliability of the results. Furthermore, the mediating effect of lifestyle factors including smoking, alcohol intake, walking, and waist-hip ratio was explored by using a two-step MR. According to our MR analysis, mood swings were genetically associated with a higher risk of CAD (OR, 2.101; 95% CI, 1.200-3.679; P = .009), AHF (OR, 2.761; 95% CI, 1.312-5.810; P = .007), and MCE (OR, 1.048; 95% CI, 1.022-1.076; P < .001). In the two-step MR analysis, smoking may mediate the causal pathways from mood swings to CAD (27%), MCE (18%), and AHF (26%). Our MR study revealed a potential causal relationship between mood swings and CVDs, smoking may play an important role in it, highlighting the need for regulating mood stability and build a healthy lifestyle to prevent the onset of CVDs. However, due to the limitations of MR, further research is needed to confirm these associations and clarify the underlying mechanisms.