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Mendelian Randomization and Transcriptomics Analysis Reveal Potential Relationships Between Lipids, Immune Cells and
Yafei Xie1, Zelin Zhang1, Yuanyuan Zhao1
1School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People's Republic of China.
International Journal of Women'S Health
|August 12, 2025
Summary
Polycystic ovary syndrome (PCOS) is linked to plasma lipids, with immune cells potentially mediating this connection. CD4+ T cells may be key mediators between lipids and PCOS, suggesting lipid management for PCOS treatment.
Area of Science:
- Genetics and Immunology
- Metabolic Disorders
Background:
- Plasma lipid levels are strongly associated with polycystic ovary syndrome (PCOS).
- Immune cells are recognized as critical indicators of lipid impact in disease progression.
- Causal evidence for immune cell mediation between lipids and PCOS remains limited.
Purpose of the Study:
- To investigate the causal relationship between plasma lipid groups and PCOS.
- To explore the mediating role of immune cells in the lipid-PCOS association.
- To examine lipid metabolism, immunity, and PCOS using transcriptome analysis.
Main Methods:
- Two-step two-sample Mendelian randomisation (TSMR) analysis.
- Inverse variance weighted (IVW) and Bayesian weighted Mendelian randomized (BWMR) methods.
- Transcriptome and metabolic inference analyses.
Main Results:
- Six plasma lipid groups causally affect PCOS; no reverse causality observed.
- Eighteen immune cell traits significantly associate with PCOS.
- CD4+ T cells, specifically SSC-A on CD4+, mediate the association between specific lipids (PC, PI) and PCOS; fatty acid biosynthesis is linked to PCOS.
Conclusions:
- Genetic and transcriptomic data support a link between lipids, immune cells, and PCOS.
- CD4+ T cells are potential key mediators in the lipid-PCOS causal pathway.
- Understanding this relationship can improve PCOS management through lipid control.
