Emotional dispositions and intracerebral hemorrhage: a Mendelian Randomization insight

Abstract

Background: Intracerebral hemorrhage (ICH) is a severe form of stroke with high mortality and limited treatment options. While traditional risk factors like hypertension have been well-studied, the role of emotional states as acute triggers for ICH remains unclear. This study employs Mendelian Randomization (MR) to investigate the causal relationship between emotional traits of worry and anxiety and the incidence of ICH.

Methods: We used a two-sample MR approach, leveraging summary-level data from genome-wide association studies (GWAS) for emotional traits and ICH. The primary analysis was conducted using the Inverse-Variance Weighted (IVW) method, supplemented by multiple sensitivity analyses including Maximum Likelihood and MR PRESSO methods.

Results: Our MR analysis revealed a robust and significant causal relationship between the emotional trait "Worrier/anxious feelings" and ICH, supported by 195 instrumental variables (SNPs). The odds ratio (OR) was 2.98 (95% CI: 1.16, 7.61) with a p-value of 0.0229. Sensitivity analyses corroborated these findings, enhancing the reliability of our results. In contrast, other emotional traits such as "Nervous feelings" and "Sensitivity/hurt feelings" did not show significant associations, reinforcing the specificity of our primary finding.

Conclusion: Our study provides compelling evidence for a causal relationship between the emotional traits of worry and anxiety and the incidence of ICH, offering a new dimension in our understanding of this devastating condition and paving the way for more nuanced risk stratification and preventive strategies.

Keywords: Mendelian randomization; anxiety; emotion; intracerebral hemorrhage; risk factor; single nucleotide polymorphisms; stroke; worry.

FIGURE 1

Flowchart of the present MR study and major assumptions.

FIGURE 2

Forest Plot Representing MR Analysis Results. This figure displays the results of the Mendelian Randomization (MR) analysis, showcasing the causal relationships between various emotional traits and the incidence of intracerebral hemorrhage (ICH).

FIGURE 3

Sensitivity Analysis. The x-axis represents the effect size between the SNPs and the exposure, while the y-axis represents the effect size between the SNPs and the outcome. Black dots represent the effect values of SNPs with both exposure and outcome, and the solid line represents the causal association between the variables and the outcome. Different colors represent different MR methods used in the analysis.

FIGURE 4

Heterogeneity Analysis. Instrumental variables from different analytical platforms, experiments, and populations may exhibit heterogeneity, thereby affecting the results of the Mendelian Randomization analysis. Heterogeneity is assessed using both IVW (Inverse-Variance Weighted) and MR-Egger tests, with a p-value <0.05 indicating the presence of heterogeneity in the study.

FIGURE 5

Forest Plot with Leave-One-Out Sensitivity Test. This figure further conducts a leave-one-out sensitivity test to check whether the causal estimates are driven by any single SNP. It reveals a consistent positive correlation between the genetic predictors and the risk of the outcome.