Dissecting the Association of Genetically Predicted Neuroticism with Coronary Artery Disease: A Two-Sample Mendelian Randomization Study

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.

Neuroticism and the Risk of Atrial Fibrillation

“…For example, neuroticism scores did not show a causal genetic association with coronary artery disease. 34 However, the genetic liability of depression is associated with a higher risk of coronary artery disease and myocardial infarction. 35 Individuals with higher levels of neuroticism also showed an increased risk of heart failure and myocardial infarction in another MR study.…”

Effect of worry, depression, and sensitivity to environmental stress owing to neurotic personality on risk of cardiovascular disease: A Mendelian randomization study

“…So far there is limited evidence from MR studies evaluating association between personality traits and CVD with mixed results. A recent MR study using instrumental variable for neuroticism comprised of 27 SNPs found causal association between neuroticism score and atrial fibrillation (Sun et al, 2021) while another MR study found no association between genetically predicted neuroticism score and coronary artery disease (Yan et al, 2022). However, in the MR analyses of individual neuroticism items, mood swings were found to genetically increase the risk of coronary artery disease (Yan et al, 2022).…”

“…A recent MR study using instrumental variable for neuroticism comprised of 27 SNPs found causal association between neuroticism score and atrial fibrillation (Sun et al, 2021) while another MR study found no association between genetically predicted neuroticism score and coronary artery disease (Yan et al, 2022). However, in the MR analyses of individual neuroticism items, mood swings were found to genetically increase the risk of coronary artery disease (Yan et al, 2022). MR analyses have also indicated the direction of causal effects from neuroticism to CVD, but not the reverse (Zhang et al, 2022).…”