Background: Observational studies have reported that individuals
diagnosed with polycystic ovary syndrome (PCOS) face a heightened vulnerability
to developing post-traumatic stress disorder (PTSD). However, it is unclear
whether this relationship is causal. Consequently, we implemented a bidirectional
Mendelian randomization (MR) analysis to examine the empirical causal association
of PCOS and PTSD. Methods: We acquired genetic association data for PCOS
through a comprehensive meta-analysis from several large-scale genome-wide
association studies (GWASs), which enrolled 10,074 cases and 103,164 controls.
For PTSD, we obtained data from a GWAS performed by the Psychiatric Genomics
Consortium Posttraumatic Stress Disorder (PGC-PTSD) group. The study included a
total of 23,212 cases of PTSD and 151,447 controls of European ancestry. For both
PCOS and PTSD, we carefully selected genetic instruments that met the rigorous
significance threshold (p 5 10, r 0.01). To investigate the causal association between PCOS and PTSD, we conducted
bidirectional Mendelian randomization (MR) analyses. The primary analysis
employed the inverse-variance weighted (IVW) method, complemented by alternative
MR approaches such as the maximum-likelihood method, MR-Egger regression,
Mendelian randomization-Robust Adjusted Profile Score (MR-RAPS), and MR
Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. Sensitivity analyses were
also carried out to verify the robustness of this association. Results:
In this study, we identified and utilized 14 genetic variants as instruments for
PCOS, while 2 genetic variants were selected as instruments for PTSD. Our
findings demonstrated that a genetic predisposition to PCOS was significantly
associated with an elevated risk of developing PTSD (odds ratio (OR) = 1.11, 95%
confidence interval (CI): 1.03–1.19, p = 7.27 10 for
IVW). MR-Egger regression analysis was performed, and the results did not provide
evidence of directional pleiotropy (p intercept = 0.187). Sensitivity
analyses utilizing alternative MR methods consistently yielded similar results,
supporting the robustness of our findings. Furthermore, in the reverse MR
analysis, we observed no significant association between genetic predisposition
to PTSD and the risk of developing PCOS (OR = 1.15, 95% CI: 0.69–1.91,
p = 0.586 for IVW). Comparable null associations were also observed when
alternative MR methods were employed. Conclusions: Through a genetic
epidemiological approach, we found that genetic predisposition to PCOS was
associated with an increased risk of PTSD, suggesting a potential causal
relationship between PCOS and PTSD. Nonetheless, further investigation is
necessary to elucidate the underlying mechanism through which PCOS contributes to
the development of PTSD.