Key result
Genetically predicted expression of nine hub genes, including CD93 (OR 1.150), significantly increased the risk of polycystic ovary syndrome, whereas PTER expression decreased the risk.
Why the study?
Polycystic ovary syndrome is a complex endocrine disorder, and understanding its underlying molecular mechanisms is essential for developing effective treatments.
Do specific hub genes causally affect the risk of developing polycystic ovary syndrome (PCOS)?
Observational (n=141,355)
Do specific hub genes causally affect the risk of developing polycystic ovary syndrome (PCOS)?
Odds Ratio: 1.15 (95% CI 1.046–1.264)
p-value: p=0.004
Bioinformatics and Mendelian randomization identified 10 hub genes causally associated with PCOS risk, providing potential novel targets for diagnosis and treatment.
These hub gene associations in PCOS are hypothesis-generating; prospective trials needed before targeting them clinically.
Background Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with various contributing factors. Understanding the molecular mechanisms underlying PCOS is essential for developing effective treatments. This study aimed to identify hub genes and investigate potential molecular mechanisms associated with PCOS through a combination of bioinformatics analysis and Mendelian randomization (MR). Methods This study employed bioinformatics analysis in conjunction with MR methods using publicly available databases to identify hub genes. We employed complementary MR methods, including inverse-variance weighted (IVW), to determine the causal relationship between the hub genes and PCOS. Sensitivity analyses were performed to ensure results reliability. Enrichment analysis and immune infiltration analysis were further conducted to assess the role and mechanisms of hub genes in the development of PCOS. Additionally, we validated hub gene expression in both an animal model and serum samples from PCOS patients using qRT-PCR. Results IVW analysis revealed significant associations between 10 hub genes and the risk of PCOS: CD93 [ P = 0.004; OR 95% CI = 1.150 (1.046, 1.264)], CYBB [ P = 0.013; OR 95% CI = 1.650 (1.113,2.447)], DOCK8 [ P = 0.048; OR 95% CI = 1.223 (1.002,1.494)], IRF1 [ P = 0.036; OR 95% CI = 1.343 (1.020,1.769)], MBOAT1 [ P = 0.033; OR 95% CI = 1.140 (1.011,1.285)], MYO1F [ P = 0.012; OR 95% CI = 1.325 (1.065,1.649)], NLRP1 [ P = 0.020; OR 95% CI = 1.143 (1.021,1.280)], NOD2 [ P = 0.002; OR 95% CI = 1.139 (1.049,1.237)], PIK3R1 [ P = 0.040; OR 95% CI = 1.241 (1.010,1.526)], PTER [ P = 0.015; OR 95% CI = 0.923 (0.866,0.984)]. No heterogeneity and pleiotropy were observed. Hub genes mainly enriched in positive regulation of cytokine production and TNF signaling pathway, and exhibited positive or negative correlations with different immune cells in individuals with PCOS. qRT-PCR validation in both the rat model and patient serum samples confirmed hub gene expression trends consistent with our combined analysis results. Conclusions Our bioinformatics combined with MR analysis revealed that CD93, CYBB, DOCK8, IRF1, MBOAT1, MYO1F, NLRP1, NOD2, PIK3R1 increase the risk of PCOS, while PTER decreases the risk of PCOS. This discovery has implications for clinical decision-making in terms of disease diagnosis, prognosis, treatment strategies, and opens up novel avenues for drug development.
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He et al. (2024) conducted an observational in Polycystic ovary syndrome (PCOS) (n=141,355). Genetically predicted expression of hub genes (e.g., CD93) vs. Control subjects was evaluated on Risk of PCOS associated with CD93 expression (OR 1.150, 95% CI 1.046, 1.264, p=0.004). Genetically predicted expression of nine hub genes, including CD93 (OR 1.150), significantly increased the risk of polycystic ovary syndrome, whereas PTER expression decreased the risk.
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