Genetic evidence for causal association between platelet count and glioma risk through Mendelian randomization analysis

Fig. 1. Mendelian randomization analysis results of platelet count and glioma risk. Forest plot of Mendelian randomization analysis examining the effect of platelet count on glioma risk. The plot displays odds ratios and 95% confidence intervals from three analytical methods (IVW radial, Maximum likelihood, and MR IVW). All methods were based on 707 SNPs, with OR < 1 indicating that increased platelet count is associated with reduced glioma risk

Fig. 2. Manhattan plot of genome-wide association study for glioma. The X-axis represents physical positions across 23 chromosomes, and the Y-axis shows association strength (-log10 P-values). Different colors represent different chromosomes, with the red dashed line indicating the genome-wide significance threshold. Data points exceeding the threshold represent genetic variants significantly associated with glioma risk

Fig. 3. Circular visualization of Mendelian randomization analysis examining associations between hematological parameters and glioma risk. The outer ring labels different hematological parameter names, while the inner ring uses color coding to represent statistical significance levels (p-values), with cyan indicating high significance (p-values approaching 0), pink indicating moderate significance, and dark red indicating low significance (p-values approaching 1)

Fig. 4. Quality control plots for Mendelian randomization analysis of platelet count and glioma risk. A Consistency validation scatter plot across multiple MR methods; B Funnel plot for detecting horizontal pleiotropy bias; C Leave-one-out sensitivity analysis; D Instrumental variable effect validation plot

Fig. 5. Genome-wide association analysis and fine-mapping of glioma. A Circular genome-wide Manhattan plot showing the distribution pattern of glioma association signals across 23 chromosomes; B Fine-mapping plot of candidate regions, displaying association strength and linkage disequilibrium patterns of SNPs within a 1 Mb window, with color coding representing linkage degree to the lead SNP

Fig. 6. Forest plot of Mendelian randomization analysis examining the effect of platelet count on glioblastoma (GBM) risk. The plot displays odds ratios and 95% confidence intervals from three statistical methods, with all approaches showing OR < 1, suggesting that increased platelet count is associated with reduced GBM risk

Fig. 7. mRNA expression levels of platelet-related genes in glioma cell lines. qRT-PCR analysis of (A) THPO, (B) GP6, (C) ITGA2B, and (D) MPL gene expression in normal human astrocytes (NHA, blue bars), U87-MG glioma cells (red bars), and U251-MG glioma cells (orange bars). Data are presented as mean ± SEM relative to NHA (normalized to 1.0). All four platelet-related genes showed significant downregulation in both glioma cell lines compared to normal astrocytes (***P < 0.001). Error bars represent standard error of the mean