Dissecting the association of genetically predicted neuroticism with pre-eclampsia: A 2-sample Mendelian randomization study

Previous observational clinical studies have found a causal relationship between neurotic personality traits and various disorders. However, the relationship between neurotic personality characteristics and pre-eclampsia (PE) is not unclear. Two-sample Mendelian randomization (MR) was employed to examine the influence of neurotic personality traits on the risk of PE. From the Finnish genome-wide database, we identified 32 single-nucleotide polymorphisms linked to neuroticism personality traits, excluding 7 confounding variables related to blood pressure and BMI. The number of tool variables associated with PE was 25. Causality was assessed using inverse variance weighting, weighted median, MR-Egger, and weighted model methods. Sensitivity analyses, such as Cochran's Q statistic, MR-Egger intercept, MR pleiotropy residual sum and outlier, and leave-one-out analysis, were conducted to identify potential heterogeneity and horizontal pleiotropy. The present 2-sample MR study did not reveal any genetic associations between neuroticism and PE. A 2-sample Mendelian randomization analysis of 12 dichotomous neuroticism items indicated that genetic predisposition to worrying elevates the risk of PE. The inverse variance weighted method produced an odds ratio (OR) of 2.23 (95% CI: 1.36-3.65, P < .05), while the weighted median analysis indicated an OR of 2.41 (95% CI: 1.20-4.85, P < .05). However, there were no significant correlations between the MR Egger and weighted modes. This study found no genetic causal link between neuroticism and PE; however, carriers may have a genetically increased risk of PE, offering a more reliable foundation for future prevention efforts.