Inflammatory factors and risk of meningiomas: a bidirectional mendelian-randomization study

Abstract

BackgroundMeningiomas are one of the most common intracranial tumors, and the current understanding of meningioma pathology is still incomplete. Inflammatory factors play an important role in the pathophysiology of meningioma, but the causal relationship between inflammatory factors and meningioma is still unclear.MethodMendelian randomization (MR) is an effective statistical method for reducing bias based on whole genome sequencing data. It’s a simple but powerful framework, that uses genetics to study aspects of human biology. Modern methods of MR make the process more robust by exploiting the many genetic variants that may exist for a given hypothesis. In this paper, MR is applied to understand the causal relationship between exposure and disease outcome.ResultsThis research presents a comprehensive MR study to study the association of genetic inflammatory cytokines with meningioma. Based on the results of our MR analysis, which examines 41 cytokines in the largest GWAS datasets available, we were able to draw the relatively more reliable conclusion that elevated levels of circulating TNF-β, CXCL1, and lower levels of IL-9 were suggestive associated with a higher risk of meningioma. Moreover, Meningiomas could cause lower levels of interleukin-16 and higher levels of CXCL10 in the blood.ConclusionThese findings suggest that TNF-β, CXCL1, and IL-9 play an important role in the development of meningiomas. Meningiomas also affect the expression of cytokines such as IL-16 and CXCL10. Further studies are needed to determine whether these biomarkers can be used to prevent or treat meningiomas.

The role of preoperative hematological inflammatory markers as a predictor of meningioma grade: A systematic review and meta-analysis

“…Tumor-associated macrophages in the tumor stroma induce immune cell responses and various cytokines. [ 49 ] Furthermore, inflammatory processes are linked to the tumor microenvironment and play a role in every stage of tumorigenesis. [ 11 ] Inflammation plays a role in tumor invasion, angiogenesis, cell proliferation, and immune cell suppression.…”

Causal relationships between systemic inflammatory cytokines and adhesive capsulitis: a bidirectional Mendelian randomization study

“…As only eight systemic inflammatory cytokines had three or more independent SNPs reaching genome-wide significance, the study adopted a less stringent threshold of 5 × 10 -6 to enhance SNP availability for inflammatory cytokines. The thresholds were used to select genetic independent variables, as described before ( 18 ). Following these steps, a total of 41 distinct types of inflammatory cytokines were identified.…”

Exploring causal correlations between inflammatory cytokines and ankylosing spondylitis: a bidirectional mendelian-randomization study

“…The GWAS data utilized in the MR analysis for 41 inflammatory factors were sourced from 8293 Finns individuals, included 41 inflammatory factors ( 12 ). GWAS data for these 41 inflammatory factors can also be found in the IEU Open GWAS project ( https://gwas.mrcieu.ac.uk/ ) with GWAS IDs, as indicated in Supplementary 1 .Summary statistics for AS were obtained from the UK Biobank, which included 186 cases and 456162 controls of European ancestry, using a generalized linear mixed model (GLMM)-based method called (fast GWA-GLMM) with adjustment for covariates ( 13 – 15 ) We performed a bidirectional two-sample MR study to assess the causality of inflammatory factors and AS, using single nucleotide polymorphisms (SNPs) as instrumental variables (IVs).These SNPs had to meet three assumptions: assumption 1: these SNPs must be strongly correlated with exposure; assumption 2: these SNPs effect on results only through exposure; assumption 3: these SNPs are not related to confounding factors ( 16 ). Figure 1 illustrates the flow chart of the entire analysis.…”