The adverse effect of mood swings on the risk of cardiovascular diseases: Evidence from Mendelian randomization analysis

Recent studies have explored the impact of personality traits, including mood swings, on physical health. However, it remains unclear whether there is a direct cause-and-effect link between mood swings and cardiovascular diseases (CVDs). A STROBE-compliant cross-sectional observational study was conducted and analyzed using a two-sample Mendelian randomization (MR) approach to examine the potential causal relationship between mood swings and a range of CVDs, such as arrhythmia, artery aneurysm, coronary heart disease (CHD), heart failure, hypertension, stroke, ischemic stroke, and peripheral artery disease. We sourced genome-wide association studies (GWAS) summary data for mood swings from the UK Biobank, and for CVDs from the GWAS Catalog and FinnGen databases. We excluded single-nucleotide polymorphisms (SNPs) linked to potential confounders such as obesity, smoking, sex, diabetes, as well as SNPs suspected of horizontal pleiotropy, as identified by MR-PRESSO and the MR-pleiotropy method, prior to the final analysis. Sensitivity analyses were conducted using the MR-Egger, inverse variance weighted, and leave-one-out methods. After screening, 57 SNPs were identified as instrumental variables for mood swings, and 9 SNPs related to confounding factors were excluded. An increase in mood swing frequency is correlated with a significant increase in the likelihood of various conditions. Notably, arrhythmia in the FinnGen dataset showed an odds ratio (OR: 2.28, 95% confidence interval [CI]: 1.44-3.61, P < .001), and atrial fibrillation had an OR (OR: 2.25, 95% CI: 1.23-4.11, P = .01). CHD risk was elevated in both the IEU OpenGWAS project (OR: 2.05, 95% CI: 1.30-3.21, P < .001) and GWAS Catalog (OR: 4.45, 95% CI: 1.75-11.33, P < .001). Increased risks were also noted for heart failure (GWAS Catalog: OR: 1.75, 95% CI: 1.09-2.83, P = .02) and hypertension (FinnGen: OR, 2.17; 95% CI: 1.47-3.19, P < .001). However, no significant associations were found for conditions such as arterial aneurysms or ischemic stroke. In combined analyses, mood swings were associated with a higher risk of CHD (OR: 2.21, 95% CI: 1.64-2.97, P < .01), heart failure (OR: 1.74, 95% CI: 1.21-2.50, P < .01), and other CVDs. This study revealed a causal link between mood swings and various CVDs, highlighting intriguing findings. This suggests that implementing proper psychological interventions to stabilize mood may be beneficial for preventing negative cardiovascular events.