Previous research has suggested that immune factors may play a significant role in female infertility, but the exact connections have not been fully understood. To explore this, this study uses Mendelian randomization (MR) to clarify the causal links between immune factors and female infertility.
Methods
The study utilized summary data from three genome-wide association studies (GWAS), which included 731 immune cell markers, 41 circulating cytokines, and five types of female infertility. The goal was to uncover the relationship between immune factors and infertility. To investigate the causal links, the study primarily used two-sample MR. It also conducted several sensitivity analyses to ensure the reliability of the results. Additionally, multivariable Mendelian randomization (MVMR) was used to explore any potential mediating effects of specific immune markers.
Results
After adjusting for false discovery rates (FDR) and conducting sensitivity analyses, the study found clear causal links between immune markers and different types of infertility. The MR analysis identified several immune markers linked to infertility subtypes:
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Higher levels of Naive CD8br% %CD8br, MIP1B, and IL17 were associated with general female infertility.
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Elevated levels of MIP1B were found to reduce the risk of ovarian infertility.
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Elevated levels of CD80 on monocytes and MIP1B increased the risk of tubal ligation.
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Three immune markers (CD86+ myeloid DC AC, HLA DR+ NK% %NK, and CD16 on CD14-CD16+ monocytes) were associated with uterine infertility.
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MIP1B, IL18, and IL17 were identified as genetic causes of cervical infertility, vaginal infertility, and other unspecified forms of infertility (FIOTHNAS).
The MVMR analysis further revealed that the effect of MIP1B on general infertility and FIOTHNAS was reduced when adjusting for the circulating levels of IL17 and IL18.
Conclusion
This study provides new insights into how immune responses contribute to the risk of female infertility through specific mechanisms for different infertility subtypes. These findings offer valuable direction for future clinical research and potential treatment options.
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