Investigating the causal associations between neuroticism, schizophrenia, and cardiovascular diseases using Mendelian
Liyuan Pu1,2, Ruijie Zhang3, Lifang Pan1,2
1Research and Education Department, Ningbo No.2 Hospital, 41 Northwest Street, Ningbo, 315010, Zhejiang, PR China.
Insights
Neuroticism increases the risk of small-vessel stroke and myocardial infarction, while schizophrenia is linked to a higher risk of heart failure, according to genetic evidence. These findings highlight the importance of mental health in cardiovascular disease prevention.
Area of Science:
- Psychiatric Genetics
- Cardiovascular Epidemiology
- Biomedical Research
Background:
- Investigating the causal links between psychological traits and cardiovascular diseases (CVDs) is crucial for public health.
- Neuroticism and schizophrenia are complex traits with potential implications for cardiovascular health.
Purpose of the Study:
- To examine the potential causal associations between neuroticism, schizophrenia, and various cardiovascular diseases using a two-sample Mendelian randomization approach.
- To determine if genetic liability to neuroticism or schizophrenia influences the risk of specific CVDs like myocardial infarction, stroke, and heart failure.
Main Methods:
- Utilized two-sample Mendelian randomization (MR) analysis with genetic variants from large genome-wide association studies (GWAS) of European ancestry.
- Employed the inverse variance-weighted (IVW) method as the primary analysis, with sensitivity analyses and multivariable MR adjusting for covariates like sleep duration and BMI.
Main Results:
- Genetically predicted neuroticism was associated with increased risk of small-vessel stroke (SVS) and myocardial infarction (MI).
- Schizophrenia showed a significant association with an elevated risk of heart failure (HF).
- These associations remained robust after multivariable MR adjustments and sensitivity analyses.
Conclusions:
- Preliminary genetic evidence suggests neuroticism is a risk factor for SVS and MI, and schizophrenia for HF.
- Findings support the integration of mental health considerations into cardiovascular disease prevention strategies.
- Identifying at-risk populations through genetic predisposition can guide targeted CVD prevention efforts.
Background:
This study employed two-sample Mendelian randomization (MR) to investigate the potential causal associations between neuroticism, schizophrenia, and various cardiovascular diseases (CVDs), including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), heart failure (HF), stroke, hemorrhagic stroke, and ischemic stroke, along with its subtypes.
Methods:
We identified independent genetic variants associated with neuroticism and schizophrenia, along with summary statistics for the instrument-outcome relationship, from the largest available genome-wide association study (GWAS) of European ancestry. The inverse variance-weighted (IVW) method was utilized as the primary analytical approach.
Results:
The IVW analysis indicated that genetically determined neuroticism was associated with an increased risk of small-vessel stroke (SVS: odds ratio [95% confidence interval] = 1.42 [1.19-1.68], P < 0.001) and MI (1.13 [1.03-1.25], P = 0.013). Furthermore, a significant association was observed between schizophrenia and HF (1.13 [1.00-1.06], P = 0.026). These associations remained significant after performing multivariable MR to adjust for sleep duration and body mass index. Specifically, the associations between genetic liability to neuroticism and both SVS and MI were statistically significant, with odds ratios of 1.26 (95% CI 1.02-1.58, P = 0.036) and 1.17 (95% CI 1.05-1.32, P = 0.006), respectively. Furthermore, the associations between schizophrenia and HF remained significant, with an odds ratio of 1.05 (95% CI 1.01-1.09, P = 0.007). These results were consistent across extensive sensitivity analyses.
Conclusion:
Our preliminary genetic evidence suggests that neuroticism may increase the risk of SVS and MI, while schizophrenia may elevate the risk of HF. These findings could inform the identification of patient populations that would benefit from CVD prevention strategies that emphasize mental health improvement.
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