Genetic evidence of the causal relationships between psychiatric disorders and cardiovascular diseases
Yanchao Wen1, Xingyu Wang1, Liufei Deng1
1Department of Health Statistics, School of Public Health, Shanxi Medical University, 56 Xin Jian South Road Street, Taiyuan, Shanxi, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan, Shanxi, China.
Insights
This study reveals bidirectional causal links between depression and myocardial infarction, and ADHD and heart failure. These findings highlight complex relationships between psychiatric disorders and cardiovascular diseases.
Area of Science:
- Genetics and Psychiatry
- Cardiovascular Medicine
- Epidemiology
Background:
- Psychiatric disorders (PDs) and cardiovascular diseases (CVDs) share risk factors and comorbidities.
- Understanding the causal relationship between PDs and CVDs is crucial for effective prevention and treatment strategies.
Purpose of the Study:
- To investigate the bidirectional causal relationships between 12 psychiatric disorders and four major cardiovascular diseases: atrial fibrillation, coronary artery disease, myocardial infarction, and heart failure.
- Utilize advanced genetic analysis methods to elucidate these complex associations.
Main Methods:
- Employed linkage disequilibrium score regression to compute genetic correlations between PDs and CVDs.
- Conducted two-sample and bidirectional Mendelian randomization (MR) analyses on phenotypes with significant genetic correlations.
- Applied multiple MR methods including modified Inverse Variance Weighted (MW-IVW) as the primary approach, with validation using the FinnGen database.
Main Results:
- Identified significant bidirectional causal relationships between depression and myocardial infarction.
- Observed similar bidirectional causal links between Attention Deficit/Hyperactivity Disorder (ADHD) and heart failure.
- Results were consistent across sensitivity analyses and validated in an independent dataset.
Conclusions:
- The study provides robust evidence for causal links between specific psychiatric disorders and cardiovascular diseases.
- Findings suggest that depression may increase the risk of myocardial infarction, and vice versa.
- Attention Deficit/Hyperactivity Disorder may causally influence heart failure risk, and vice versa, underscoring the intricate interplay between mental health and cardiac well-being.
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.
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