Abstract
Background: Observational studies on the association between neuroticism and coronary artery disease (CAD) are still rare, and the results of existing studies are not consistent. The present study aimed to explore causal associations of neuroticism with CAD. Methods: The summary-level data of GWAS for neuroticism and 12 items used to assess neuroticism were extracted from the UK Biobank, and included up to 380,506 participants. The general data for CAD were obtained from the CARDIoGRAMplusC4D consortium, which assembled 60,801 CAD patients and 123,504 non-cases. Single-nucleotide polymorphisms associated with neuroticism and 12 items at genome-wide significance were explored as instrumental variables. Two-sample Mendelian randomization (TSMR) analyses were performed to evaluate causal associations amongst the genetically predicted neuroticism and 12 items with CAD. Results: The present TSMR study did not reveal the genetic association of neuroticism with CAD. The calculated ORs for CAD using inverse-variance weighted, weighted median, and MR-Egger analysis were 1.12 (p-value = 0.187), 0.99 (p-value = 0.943), and 0.82 (p-value = 0.683), respectively. Further TSMR analysis of 12 dichotomous items for assessing neuroticism suggested that mood swings genetically increased the risk of CAD (OR = 1.67, p-value < 0.001). Conclusions: This study reported no genetically causal association of neuroticism with CAD. The present study also found that mood swings may genetically increase the risk of CAD. These findings may highlight the potential of mood control as a preventive measure for CAD.
Highlights
Introduction iationsNeuroticism involves a pattern of irritability, anger, sadness, anxiety, worry, hostility, self-consciousness, and vulnerability [1,2], which reflects the process of individual emotion regulation and the tendency to experience negative emotions and emotional instability, which has far-reaching implications for public health [3]
Given the uncertainties about the causal role of neuroticism for coronary artery disease (CAD), we aimed to evaluate the potential causal association of neuroticism with CAD using two-sample Mendelian randomization (TSMR) analysis
We conducted a Two-sample Mendelian randomization (TSMR) analysis assessing the causal effect of neuroticism in the development of CAD
Summary
Introduction iationsNeuroticism involves a pattern of irritability, anger, sadness, anxiety, worry, hostility, self-consciousness, and vulnerability [1,2], which reflects the process of individual emotion regulation and the tendency to experience negative emotions and emotional instability, which has far-reaching implications for public health [3]. Coronary artery disease (CAD) is one of the most common cardiovascular diseases in the clinic, greatly increasing the burden on both patients and public health [13]. The present study aimed to explore causal associations of neuroticism with CAD. Results: The present TSMR study did not reveal the genetic association of neuroticism with CAD. Further TSMR analysis of 12 dichotomous items for assessing neuroticism suggested that mood swings genetically increased the risk of CAD (OR = 1.67, p-value < 0.001). The present study found that mood swings may genetically increase the risk of CAD. These findings may highlight the potential of mood control as a preventive measure for CAD
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