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

Area of Science:

• Genetics
• Epidemiology
• Women's Health

Background:

• Gynecological disorders present significant global health challenges.
• Observational studies suggest a link between mood instability and female diseases, but causality is unproven.
• Mendelian randomization (MR) is employed to investigate potential causal relationships.

Purpose of the Study:

• To explore the genetically predicted causal relationship between mood swings and prevalent gynecological disorders.
• To address limitations of observational studies regarding causality.
• To provide insights for improving patient outcomes in gynecological health.

Main Methods:

• Utilized UK Biobank data for mood swing instrumental variables (IVs) from over 200,000 cases and controls.
• Obtained genetic variants for gynecological disorders from GWASs and the FinnGen consortium.
• Applied robust analytical methods, including inverse variance weighting (IVW), and assessed pleiotropy, sensitivity, and heterogeneity in a European population.

Main Results:

• Mood swings showed a significant positive association with endometrial cancer (OR=2.60), cervical cancer (OR=1.01), and endometriosis (OR=2.58) via the IVW method.
• No causal relationship was found between mood swings and ovarian cancer.
• Analytical methods confirmed no significant pleiotropy or heterogeneity, and sensitivity tests were passed.

Conclusions:

• Mood swings may be a genetically predicted causal risk factor for endometrial cancer, cervical cancer, and endometriosis in Europeans.
• Findings offer a genetically informed perspective, overcoming observational study limitations.
• The focus on European populations may limit global generalizability.