Causal Relationship Between Mood Swing and Gynecological Disorders: A Mendelian Randomization Study

Jia Bian, Hongfeng Li, Yaping Shang, Fang Zhang, Lifei Tang Department of Gynecology and Obstetrics, The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of ChinaCorrespondence: Jia Bian, Department of Gynecology and Obstetrics, The Affiliated People’s Hospital of Ningbo University, 251# East Baizhang Road, Ningbo, Zhejiang, 315040, People’s Republic of China, Email nbjiabian@126.comBackground: Gynecological disorders are a wide range of health problems affecting the female reproductive system, which poses substantial health challenges worldwide. Increasing number of observational studies have associated mood instability to common female diseases, but the underlying causal relationship remains unclear. In this work, Mendelian randomization (MR) analysis was applied to explore the genetically predicted causal relationship of mood swings and several prevalent gynecological disorders.Methods: Instrumental variables (IVs) of mood swings were selected from UK Biobank (UKB), with 204,412 cases and 247,207 controls being incorporated. The genetic variants for female disorders were obtained from genome-wide association studies (GWASs) and FinnGen consortium. To avoid biases caused by racial difference, only European population was included here. Five strong analytical methodologies were used to increase the validity of the results, the most substantial of which was the inverse variance weighting (IVW) method. Pleiotropy, sensitivity, and heterogeneity were assessed to strengthen the findings.Results: We found mood swings was significantly positively associated with risk of endometrial cancer (OR= 2.60 [95% CI= 1.36, 4.95], P= 0.0037), cervical cancer (OR= 1.01[95% CI= 1.00,1.02], P= 0.0213) and endometriosis (OR= 2.58 [95% CI= 1.18, 5.60], P= 0.0170) by IVW method. However, there was no causal relationship between mood swing and ovarian cancer. No pleiotropy and heterogeneity existed and sensitivity tests were passed.Conclusion: This study reveals that mood swing may serve as a genetically predicted causal risk factor for endometrial cancer, cervical cancer, and endometriosis in the European population, while no such association was observed for ovarian cancer. These findings make up for observational research’s inherent limitations and may improve patient outcomes in the field of gynecological health. However, the study’s focus on European populations may limit the applicability of these results globally.Keywords: Mendelian randomization, mood swing, genetic relationship, gynecological disorders