Genetic evidence of the causal relationships between psychiatric disorders and cardiovascular diseases

Objective: Our primary objective is to investigate the causal relationships between 12 psychiatric disorders (PDs) and atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), and heart failure (HF).

Methods: Firstly, we used linkage disequilibrium score regression to calculate the genetic correlations between 12 PDs and 4 cardiovascular diseases (CVDs). Subsequently, we performed two-sample and bidirectional Mendelian randomization (MR) analyses of phenotypes with significant genetic correlations to explore the causal relationships between PDs and CVDs. Inverse variance weighted with modified weights (MW-IVW), Robust Adjusted Profile Score, Inverse Variance Weighted, weighted median and weighted mode were used to evaluate causal effects, with MW-IVW being the main analysis method. And to validate the MR results, we conducted the replicate analyses using data from the FinnGen database.

Results: Conducting MR analyses in phenotypes with significant genetic correlations, we identified bidirectional causal relationships between depression (DEP) and MI (DEP as exposure: OR = 1.1324, 95 % confidence interval (CI): 1.0984-1.1663, P < 0.0001; MI as exposure: OR = 1.0268, 95 % CI: 1.0160-1.0375, P < 0.0001). Similar relationships were observed in Attention Deficit/Hyperactivity Disorder (ADHD) and HF (ADHD as exposure: OR = 1.0270, 95 % CI: 1.0144-1.0395, P < 0.0001; HF as exposure: OR = 1.0980, 95 % CI: 1.0502-1.1458, P < 0.0001).

Conclusions: In our study, we conducted the comprehensive analyses between 12 PDs and CVDs. By bidirectional MR analysis, we observed significant causal relationships between MI and DEP, HF and ADHD. These findings suggest possible complex causal relationships between PDs and CVDs.