心房颤动与乳腺癌的双向两样本孟德尔随机化研究
Bidirectional two-sample Mendelian randomization study of atrial fibrillation and breast cancer.
作者信息
Ding Fan, Chen Chen, Wang Yuling, Zhu Tingting, Jiao Linke, Shen Zihuan, Zhang Zhiwei, Lv Lifei, Cui Xiangning, Lu Yingdong
机构信息
Department of Cardiovascular Unit, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Graduate School of Beijing University of Chinese Medicine, Beijing, China.
出版信息
Front Cardiovasc Med. 2024 Nov 25;11:1434963. doi: 10.3389/fcvm.2024.1434963. eCollection 2024.
BACKGROUND
Observational studies have shown an association between Breast Cancer (BC) and Atrial Fibrillation (AF). However, due to confounding factors and reverse causality, the causal role between BC and AF remains unclear. In this study, bidirectional two-sample Mendelian randomization (MR) combined with meta-analysis was used to evaluate the causal association between BC and AF.
METHODS
Based on the Genome-Wide Association Studies (GWAS) summary data sets, the Inverse variance weighted (IVW) method was used as the main method, the weighted median method and MR-Egger method were used for Bidirectional Two-Sample Mendelian Randomization, and the Egger intercept test was used to detect horizontal pleiotropy. Heterogeneity was tested by Cochran's Q test, and sensitivity analysis was performed by "leave-one-out". GWAS data for AF and BC were obtained from three separate databases (FinnGen, UKBiobank, GWAScatalog) for European individuals. Finally, meta-analysis was performed on the MR Analysis results from different databases.
RESULTS
The pooled IVW results showed no evidence of an effect of BC on the risk of AF (IVW: OR = 0.9994; 95% CI = 0.9967-1.0022). There was also no evidence of an effect of AF on BC risk (IVW: OR = 0.9970; 95% CI = 0.9154-1.0859).
CONCLUSION
The results of the Bidirectional Two-Sample Mendelian Randomization study show that there is no causal relationship between BC and AF.
背景
观察性研究表明乳腺癌（BC）与心房颤动（AF）之间存在关联。然而，由于混杂因素和反向因果关系，BC与AF之间的因果作用仍不明确。在本研究中，采用双向两样本孟德尔随机化（MR）结合荟萃分析来评估BC与AF之间的因果关联。
方法
基于全基因组关联研究（GWAS）汇总数据集，采用逆方差加权（IVW）法作为主要方法，加权中位数法和MR-Egger法用于双向两样本孟德尔随机化，Egger截距检验用于检测水平多效性。通过Cochran's Q检验检测异质性，并采用“留一法”进行敏感性分析。AF和BC的GWAS数据来自欧洲个体的三个独立数据库（芬兰基因库、英国生物银行、GWAS目录）。最后，对不同数据库的MR分析结果进行荟萃分析。
结果
汇总的IVW结果显示，没有证据表明BC对AF风险有影响（IVW：OR = 0.9994；95% CI = 0.9967 - 1.0022）。也没有证据表明AF对BC风险有影响（IVW：OR = 0.9970；95% CI = 0.9154 - 1.0859）。
结论
双向两样本孟德尔随机化研究结果表明，BC与AF之间不存在因果关系。
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