■静脉曲张(VV)是一种常见的慢性静脉疾病,受多种因素影响。它影响患者的生活质量,并给医疗保健系统带来巨大的经济负担。本研究旨在采用综合分析方法,包括孟德尔随机化分析,确定VV治疗的潜在致病基因和药物靶标。
■这项研究对从全基因组关联研究和顺式表达数量性状基因座数据库收集的数据进行了基于摘要数据的孟德尔随机化(SMR)分析和共定位分析。只有带有PP的基因。从显著的SMR结果中选择H4>0.7的共定位。经过以上分析,我们筛选了12个基因,并对其进行了孟德尔随机化(MR)分析.经过敏感性分析,我们确定了4个与VV有潜在因果关系的基因.最后,我们使用全转录组关联研究和药物-基因相互作用数据库数据来鉴定和筛选其余基因,并确定了治疗VV的4个药物靶点.
■我们确定了四个与VV显著相关的基因,即,KRTAP5-AS1[赔率比(OR)=1.08,95%置信区间(CI):1.05-1.11,p=1.42e-10]和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)和CRIM1(OR=0.87,95%CI:0.81-0.95,p=3.67e-3)。三个基因的表达增加,即,KRTAP5-AS1,PLEKHA5和CBWD1与该疾病的风险增加有关,CRIM1表达增加与疾病风险降低相关。这四个基因可以被靶向用于VV治疗。
■我们用MR鉴定了四种潜在的静脉曲张致病蛋白。综合分析表明,KRTAP5-AS1,PLEKHA5,CBWD1和CRIM1可能是静脉曲张的潜在药物靶标。
UNASSIGNED: Varicose veins (VV) are 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.
UNASSIGNED: This study conducted Summary-data-based Mendelian Randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies and cis-expression quantitative trait loci databases. Only genes with PP.H4 > 0.7 in colocalization were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization (MR) analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies and The Drug-Gene Interaction Database data to identify and screen the remaining genes and identified four drug targets for the treatment of VV.
UNASSIGNED: We identified four genes significantly associated with VV, namely, KRTAP5-AS1 [Odds ratio (OR) = 1.08, 95% Confidence interval (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.
UNASSIGNED: We identified four potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that KRTAP5-AS1, PLEKHA5, CBWD1, and CRIM1 might be potential drug targets for varicose veins.