We employed an integrated bioinformatics screening approach along with Mendelian randomization (MR) analysis to explore potential genetic targets for varicose veins of lower extremities (VVs) and identify potential treatment options for VVs. Differential expression analysis was conducted using R software to identify differentially expressed genes (DEGs) of VVs from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression networks. Functional enrichment analyses were conducted for the identified genes. A protein–protein interaction network was constructed to analyze the interactions among the identified genes. Additionally, genome-wide association studies data for VVs were downloaded for MR analysis. Various methods, including inverse-variance weighted, were employed to assess potential causal associations with VVs risk, followed by sensitivity analysis. The DEGs identified from the VVs Gene Expression Omnibus dataset included 180 upregulated genes and 335 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that the downregulated DEGs were significantly associated with nuclear protein-containing complexes and nucleic acid binding ( P .05). “Leave-one-out” validation analysis did not indicate any changes. Our study unveils the involvement of ENOX2 and the related mechanisms in the pathogenesis of VVs, suggesting their potential as genetic targets for treatment.
He et al. (Fri,) studied this question.