摘要
目的:利用全基因组关联研究（GWAS）分析相关数据，通过两样本孟德尔随机化（MR）评估阑尾切除与结直肠肛管恶性肿瘤发生之间的因果关系。方法:阑尾切除与结直肠肛管恶性肿瘤相关的单核苷酸多态性（SNP）数据来自英国生物数据库（UK Biobank）和GWAS catalog生物数据库，筛选与阑尾切除密切关联的遗传位点作为工具变量，分别以MR-Egger回归法、加权中位数法、逆方差加权法进行MR分析，以P值评价阑尾切除和结直肠肛管恶性肿瘤风险之间的因果关系。结果:最终筛选出15个与阑尾切除相关的SNP位点作为最终工具变量，即rs106520、rs10829663、rs10849448、rs142069498、rs21525、rs2171591、rs224029、rs2326394、rs2780304、rs34236350、rs56259011、rs72827881、rs7649870、rs76896900、rs815430。以三种方法进行MR分析，皆显示P>0.05，阑尾切除与结直肠肛管恶性肿瘤之间没有因果关系，数据之间的异质性和总体多效性不明显。结论:阑尾切除与结直肠肛管恶性肿瘤发生风险没有相关的遗传证据。
Abstract
Objective:To reveal the causal association between appendicectomy and colorectal anal canal malignancies, by conducting a two-sample Mendelian randomization (MR) analysis using Genome Wide Association Study (GWAS).Methods:The single nucleotide polymorphism (SNP) data associated with appendectomy and colorectal anal malignancies were obtained from publicly published biological databases such as UK Biobank and GWAS catalog, and all aggregated data based on GWAS were analyzed. Genetic loci closely associated with appendectomy were selected as instrumental variables. MR-Egger regression method, weighting median method, inverse variance weighting method were used to make two-sample MR, and P-value was used to evaluate the causal relationship between appendectomy and the risk of colorectal and anal canal malignancy.Results:15 SNP loci related to appendicectomy were screened, including rs106520, rs10829663, rs10849448, rs142069498, rs21525, rs2171591, rs224029, rs2326394, rs2780304, rs34236350, rs56259011, rs72827881, rs7649870, rs76896900, rs815430. Three MR analysis methods revealed that there was no causal relationship between appendicectomy and colorectal anal canal malignancies. The heterogeneity and overall pleiotropy between data were not significant (P>0.05).Conclusion:There is no causal relationship between appendicectomy and colorectal anal canal malignancies.
万方数据