Causal relationship between genetically predicted antibody-Mediated Immune Responses and female infertility.

OBJECTIVE

This study aims to explore the causal relationship between Antibody-Mediated Immune Response (AIR) and female infertility using Mendelian randomization analysis, providing new targets and insights for treating female infertility.

METHODS

Exposure data from a genome-wide association study (GWAS) involving 9724 participants provided information on 46 types of AIR. Outcome data were sourced from a large-scale meta-analysis of female infertility, which included 899 cases and 246,641 controls. Five different Mendelian randomization analysis methods were used to assess the genetic causal relationship between AIR and female infertility, with the inverse variance-weighted method as the primary approach. The robustness of the study results was evaluated through heterogeneity analysis, pleiotropy tests, and leave-one-out validation. Replication and meta-analysis were conducted using FinnGen data to further identify AIR.

RESULTS

Through rigorous genetic variant screening, IVW, sensitivity analysis, replication, and meta-analysis, the results indicate that only seropositivity of anti-polyomavirus 2 IgG shows significant evidence of association with female infertility. The reverse MR analysis did not reveal a genetic causal association between female infertility and this antibody-influencing relationship. Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. Replication and meta-analysis using FinnGen data further supported that only anti-polyomavirus 2 IgG seropositivity has a significant association with female infertility.

CONCLUSION

Using Mendelian randomization analysis in two independent samples, this study presents evidence of a genetic association between anti-polyomavirus 2 IgG seropositivity and female infertility. These findings carry significant implications for the prevention and treatment of female infertility in clinical practice.