Background
The causality between neuroticism, a personality trait characterized by the tendency to experience negative emotions, and female reproductive diseases remains unclear. To provide evidence for the development of effective screening and prevention strategies, this study employed Mendelian randomization (MR) to investigate the causality between neuroticism clusters and female reproductive diseases.
Methods
Instrumental variables were obtained from large-scale genome-wide association studies of populations of European descent involving three neuroticism clusters (depressed affect, worry, sensitivity to environmental stress, and adversity [SESA]) in the Complex Trait Genetics database and six female reproductive diseases (infertility, polycystic ovary syndrome [PCOS], spontaneous abortion, recurrent spontaneous abortion, endometriosis, and uterine fibroids) in the FinnGen database. The bidirectional two-sample MR analysis was conducted using the inverse variance-weighted, weighted median, and MR-Egger methods, whereas the sensitivity analysis was conducted using the Cochran’s Q-test, MR-Egger intercept, and leave-one-out analysis.
Results
In the forward analysis, genetically predicted depressed affect and worry components of neuroticism significantly increased the risk of infertility (depressed affect: odds ratio [OR] = 1.399, 95% confidence interval [CI]: 1.054–1.856,
p
= 0.020; worry: OR = 1.587, 95% CI: 1.229–2.049,
p
= 0.000) and endometriosis (depressed affect: OR = 1.611, 95% CI: 1.234–2.102,
p
= 0.000; worry: OR = 1.812, 95% CI: 1.405–2.338,
p
= 0.000). Genetically predicted SESA component of neuroticism increased only the risk of endometriosis (OR = 1.524, 95% CI: 1.104–2.103,
p
= 0.010). In the reverse analysis, genetically predicted PCOS was causally associated with an increased risk of the worry component of neuroticism (Beta = 0.009, 95% CI: 0.003–0.016,
p
= 0.003).
Conclusions
The MR study showed that the three neuroticism personality clusters had definite causal effects on at least one specific female reproductive disease. Moreover, PCOS may increase the risk of the worry component of neuroticism. This finding suggests the need to screen for specific female reproductive diseases in populations with high neuroticism and assess the psychological status of patients with PCOS.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12905-024-03347-x.