Identifying Potential Drug Targets for Varicose Veins through Integration of GWAS and eQTL Summary Data

Abstract

BackgroundVaricose veins (VV) is a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment. MethodsThis study conducted summary-data-based Mendelian randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies (GWASs) and cis-expression quantitative trait loci (cis-eQTL) databases. Only genes with PP. H4 > 0.7 were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies (TWAS) analysis and The Drug-Gene Interaction Database (DGIdb, https://dgidb.org)data to identify and screen the remaining genes and identified four drug targets for the treatment of VV. ResultsWe identified four genes significantly associated with VV, namely KRTAP5-AS1 (OR = 1.08, 95% CI: 1.05-1.11, p = 1.42e-10) and PLEKHA5 (OR = 1.13, 95% CI: 1.06-1.20, p = 6.90e-5), CBWD1 (OR = 1.05, 95% CI: 1.01-1.11, p = 1.42e-2) and CRIM1 (OR = 0.87, 95% CI: 0.81-0.95, p = 3.67e-3). Increased expression of three genes, namely KRTAP5-AS1, PLEKHA5, and CBWD1, was associated with increased risk of the disease, and increased expression of CRIM1 was associated with decreased risk of the disease. These four genes could be targeted for VV therapy. ConclusionThis study identified four drug targets for potential treatment of VV, and the results may contribute to improving the quality of life of VV patients.