活产数量与乳腺癌因果关系:双样本孟德尔随机化

Causal Relationship between Number of Live Births and Breast Cancer: Two Sample Mendelian Randomisation Analysis

目的:本研究旨在应用双样本孟德尔随机化分析研究欧洲人群中活产数量与乳腺癌发病率之间的因果关系。方法:在开放GWAS网站中获得暴露因素GWAS ID,筛选与暴露相关的SNP且去除连锁不平衡,将去除与混杂因素及结局相关的SNPs作为工具变量。提取结局中与工具变量相关的SNPs并去除回文序列。进行双样本孟德尔随机化,得到初步结果。检测异质性及离群值,剔除离群的SNPs。计算beta值和标准误(SE),并将beta值转换成OR值,并计算beta和OR的95%置信区间。结果:双样本孟德尔随机化分析得到数据活产数量(OR: 0.778, 95%CI: 0.655~0.925, P = 0.005)。结论:活产数量与乳腺癌存在因果关系,并且存在负向因果,即活产数量越多乳腺癌发病率越低。

Objective: The aim of this study was to investigate the causal relationship between the number of live births and the incidence of breast cancer in a European population using two-sample Mendelian randomization analysis. Methods: The exposure factor GWAS ID was obtained from the open GWAS website, the SNPs associated with exposure were screened and the linkage disequilibrium was removed, and the SNPs associated with confounders and outcomes were removed as instrumental variables. The SNPs associated with instrumental variables in the outcome were extracted and the palindromic sequence was removed. Two-sample Mendelian randomization was performed to obtain preliminary results. Heterogeneity and outlier values were detected, and outlier SNPs were eliminated. Compute beta values and standard errors (SE), and convert beta values to OR values, and compute 95% confidence intervals for beta and OR. Results: The number of live births was obtained by two-sample Mendelian randomization (OR: 0.778, 95%CI: 0.655~0.925, P = 0.005). Conclusion: There is a causal relationship between the number of live births and breast cancer, and there is a negative causal relationship, that is, the higher the number of live births, the lower the incidence of breast cancer.