Complex Causal Association between Immunophenotypes and Adenomyosis: univariable, bidirectional, and multivariable Mendelian randomization

Elsevier

Available online 2 June 2025, 104551

Journal of Reproductive ImmunologyAuthor links open overlay panel, , , , , Highlights•

MR study links 16 immunophenotypes to adenomyosis positively.

10 immunophenotypes negatively associated with adenomyosis.

Reverse MR shows 16 positive and 4 negative correlations.

Multivariable MR identifies 5 risk factors and 8 protective factors.

Study offers insights for clinical research on adenomyosis.

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.

AbbreviationsMR

Mendelian randomization

IVW

inversewide association study

TBNK

T cells, B cells, natural killer cells

MFIs

median fluorescence intensities

MPs

morphological parameters

SNPs

single nucleotide polymorphism

MVMR

multivariate Mendelian randomization

Keywords

Mendelian randomization

adenomyosis

immune cells

natural killer cell

macrophage

© 2025 The Author(s). Published by Elsevier B.V.

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