Complex causal association between immunophenotypes and adenomyosis: Univariable, bidirectional, and multivariable Mendelian randomization

Qi Wu; Wenwen Shao; Jia Zhen; Ze Li; Ziyuan Zhao; Wei Shi

doi:10.1016/j.jri.2025.104551

Complex causal association between immunophenotypes and adenomyosis: Univariable, bidirectional, and multivariable Mendelian randomization

J Reprod Immunol. 2025 Jun 2:170:104551. doi: 10.1016/j.jri.2025.104551. Online ahead of print.

Authors

Qi Wu¹, Wenwen Shao¹, Jia Zhen¹, Ze Li², Ziyuan Zhao¹, Wei Shi³

Affiliations

¹ First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Shandong, China.
² Health Sciences, Shandong University of Traditional Chinese Medicine, Shandong, China.
³ Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong, China. Electronic address: sw19781214@163.com.

PMID: 40505456
DOI: 10.1016/j.jri.2025.104551

Abstract

This study aimed to explore the causal link between immunophenotypes and adenomyosis using Mendelian randomization (MR). We conducted a bidirectional MR analysis on 731 immunophenotypes, employing inverse-variance weighted (IVW) as the primary method, supplemented by MR-Egger, weighted mode, and weighted median analyses. Sensitivity analyses were performed to ensure result robustness. Multivariable MR was also used to control for confounding among immune cells. Results showed that 16 immunophenotypes were positively associated with adenomyosis (p < 0.05, OR > 1), while 10 had a negative correlation (p < 0.05, OR < 1). Reverse MR revealed 16 positive and 4 negative correlations with adenomyosis (P < 0.05, OR > 1 or < 1). Multivariable MR identified 5 risk factors and 8 protective factors for adenomyosis (P < 0.05, OR > 1 or < 1). This study clarifies the significant correlation between immune cells and adenomyosis, offering valuable insights for future clinical research.

Keywords: Adenomyosis; Immune cells; Macrophage; Mendelian randomization; Natural killer cell.