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Genetic evidence reveals phosphatidylcholine as a mediator in the causal relationship between omega-3 and multiple

Jian Li1,2, Youxuan Li3, Jun Wang3

  • 1The First College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, No. 71, Baoshan North Road, Yunyan District, Guiyang, 550001, Guizhou Province, China.

Scientific Reports
|August 8, 2025
PubMed

Insights

Omega-3 fatty acids may reduce the risk of multiple myeloma (MM). This Mendelian randomization study found a causal link, potentially mediated by phosphatidylcholine, suggesting a new prevention strategy for MM.

Area of Science:

  • Nutritional Epidemiology
  • Genetic Epidemiology
  • Cancer Research

Background:

  • Observational studies suggest omega-3 fatty acids may lower cancer risk.
  • The specific association between omega-3 intake and multiple myeloma (MM) incidence requires clarification.

Purpose of the Study:

  • To investigate the causal relationship between omega-3 fatty acids and MM risk using Mendelian randomization (MR).
  • To explore the potential mediating role of plasma lipids in the omega-3 and MM association.

Main Methods:

  • Two-sample and multivariate Mendelian randomization (MR) analyses were performed using large-scale genome-wide association study (GWAS) data.
  • Meta-analysis of MR results from four independent omega-3 GWAS datasets.
  • Two-step MR was utilized to identify potential lipid mediators.

Main Results:

  • Meta-analysis of MR results indicated that genetically predicted higher omega-3 levels are associated with a reduced risk of MM (OR=0.80, P<0.001).
  • Multivariate MR confirmed this inverse association after adjusting for obesity and type 2 diabetes.
  • Phosphatidylcholine (18:2_20:4) was identified as a potential mediator in the omega-3-MM pathway.

Conclusions:

  • Omega-3 fatty acids appear to causally reduce the risk of developing multiple myeloma.
  • Increased levels of phosphatidylcholine (18:2_20:4) may mediate the protective effect of omega-3 on MM.
  • Findings offer potential new avenues for MM prevention and treatment strategies.
Keywords:
Causal associationMendelian randomizationMultiple myelomaOmega-3

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