Causal association between Neuroticism and risk of aortic aneurysm: A bidirectional two-sample Mendelian randomization study

Background: The objective of this study was to analyze the causal relationship between Neuroticism and aortic aneurysm using Mendelian randomization (MR). The study aimed to establish a foundation for the development of effective prevention and treatment strategies. Methods: Genetic association data for Neuroticism were obtained from the UK Biobank, which included 393,411 individuals and 11,968,760 single nucleotide polymorphisms (SNPs). Genetic association data for aortic aneurysm were obtained from a genome-wide association study (GWAS), which included 479,194 individuals and 24,191,825 SNPs. Heterogeneity was assessed using the Cochran's Q statistic test. The study also utilized the MR Pleiotropy RESidual Sum and Outlier (Mr-PRESSO) test, as well as the MR-Egger regression method, to examine horizontal pleiotropy and determine the reliability of the findings through the leave-one-out method. Results: Forward MR analysis showed that the risk of aortic aneurysm was elevated in individuals with genetically predicted Neuroticism compared to those without Neuroticism (OR = 1.1315, 95 % CI: 1.0269-1.2468; P = 0.0126). The Cochran's Q test showed no heterogeneity (P > 0.05), and the MR-PRESSO test did not identify instrumental variables of horizontal pleiotropy (P > 0.05). The MR analysis remained robust after removing SNPs one by one. Inverse MR analysis did not observe an association between aortic aneurysm and having Neuroticism OR = 1.030, 95 % CI: 0.9459-1.118, P = 0.488). Conclusion: Our study has established a clear causal relationship between genetically determined Neuroticism and the development of aortic aneurysms. It is therefore important to intensify screening and prevention efforts for aortic aneurysms in neurotic patients. It also opens new avenues for exploring the disease's pathogenesis.