The causal association between systemic inflammatory regulators and primary ovarian insufficiency: a bidirectional...

Area of Science:

• Reproductive Endocrinology
• Immunology
• Genetics

Background:

• Emerging evidence suggests a link between systemic inflammatory regulators and primary ovarian insufficiency (POI).
• A clear causal relationship between these factors remains to be established.
• This study investigates the potential causal link using a robust genetic approach.

Purpose of the Study:

• To explore the causal relationship between 41 systemic inflammatory regulators and the risk of primary ovarian insufficiency (POI).
• To utilize a bidirectional, two-sample Mendelian randomization (MR) strategy for robust causal inference.
• To identify specific inflammatory markers associated with POI risk.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design.
• Utilized large-scale genome-wide association study data for 41 systemic inflammatory regulators and POI from the FinnGen consortium.
• Applied multiple MR methods (inverse variance weighting, Maximum Likelihood, MR-Egger, Weighted Median, etc.) and assessed heterogeneity and pleiotropy.

Main Results:

• Lower levels of vascular endothelial growth factor (VEGF) were associated with an increased risk of POI (OR=0.73).
• Decreased levels of interleukin-10 (IL-10) were significantly linked to a higher risk of POI (OR=0.54).
• Reverse MR analysis indicated no significant causal effect of POI on the expression of the studied inflammatory regulators; no significant heterogeneity or pleiotropy was detected.

Conclusions:

• Established a causal association between specific systemic inflammatory regulators and POI.
• Identified reduced VEGF and IL-10 levels as risk factors for developing POI.
• Suggests potential for VEGF and IL-10 as early biomarkers for POI prediction, prevention, and therapeutic targeting.