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Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
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In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
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Complex causal association between immunophenotypes and adenomyosis: Univariable, bidirectional, and multivariable

Qi Wu1, Wenwen Shao1, Jia Zhen1

  • 1First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Shandong, China.

Journal of Reproductive Immunology
|June 12, 2025
PubMed
Summary

This study used Mendelian randomization to investigate the causal link between immune cell profiles and adenomyosis. Findings reveal significant positive and negative associations, identifying potential risk and protective factors for adenomyosis.

Keywords:
AdenomyosisImmune cellsMacrophageMendelian randomizationNatural killer cell

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Area of Science:

  • Immunology
  • Genetics
  • Reproductive Medicine

Background:

  • Adenomyosis is a complex gynecological condition with unclear etiology.
  • The role of immune system dysregulation in adenomyosis pathogenesis is increasingly recognized.

Purpose of the Study:

  • To explore the causal relationship between various immunophenotypes and adenomyosis using a robust Mendelian randomization approach.
  • To identify specific immune cell types that may act as risk or protective factors for adenomyosis.

Main Methods:

  • Bidirectional Mendelian randomization (MR) analysis was performed on 731 immunophenotypes.
  • Inverse-variance weighted (IVW) was the primary analysis method, with MR-Egger, weighted mode, and weighted median as sensitivity analyses.
  • Multivariable MR was employed to account for confounding factors among immune cells.

Main Results:

  • Significant associations were found between 16 immunophenotypes and increased risk of adenomyosis (p < 0.05, OR > 1).
  • Conversely, 10 immunophenotypes were associated with a decreased risk of adenomyosis (p < 0.05, OR < 1).
  • Reverse MR and multivariable MR further identified specific immune cell-related risk (5 factors) and protective (8 factors) associations.

Conclusions:

  • This study establishes a significant correlation between specific immunophenotypes and adenomyosis.
  • The findings provide valuable etiological insights and potential targets for future clinical research and therapeutic interventions in adenomyosis.