孟德尔随机化
乳腺癌
人体测量学
相关性
工具变量
前列腺癌
样本量测定
因果推理
统计
人口学
医学
肿瘤科
癌症
生物
内科学
遗传学
数学
基因型
遗传变异
社会学
基因
几何学
作者
Yixin Gao,Jinhui Zhang,Huashuo Zhao,Fengjun Guan,Ping Zeng
标识
DOI:10.3389/fgene.2021.651332
摘要
In two-sample Mendelian randomization (MR) studies, sex instrumental heterogeneity is an important problem needed to address carefully, which however is often overlooked and may lead to misleading causal inference.We first employed cross-trait linkage disequilibrium score regression (LDSC), Pearson's correlation analysis, and the Cochran's Q test to examine sex genetic similarity and heterogeneity in instrumental variables (IVs) of exposures. Simulation was further performed to explore the influence of sex instrumental heterogeneity on causal effect estimation in sex-specific two-sample MR analyses. Furthermore, we chose breast/prostate cancer as outcome and four anthropometric traits as exposures as an illustrative example to illustrate the importance of taking sex heterogeneity of instruments into account in MR studies.The simulation definitively demonstrated that sex-combined IVs can lead to biased causal effect estimates in sex-specific two-sample MR studies. In our real applications, both LDSC and Pearson's correlation analyses showed high genetic correlation between sex-combined and sex-specific IVs of the four anthropometric traits, while nearly all the correlation coefficients were larger than zero but less than one. The Cochran's Q test also displayed sex heterogeneity for some instruments. When applying sex-specific instruments, significant discrepancies in the magnitude of estimated causal effects were detected for body mass index (BMI) on breast cancer (P = 1.63E-6), for hip circumference (HIP) on breast cancer (P = 1.25E-20), and for waist circumference (WC) on prostate cancer (P = 0.007) compared with those generated with sex-combined instruments.Our study reveals that the sex instrumental heterogeneity has non-ignorable impact on sex-specific two-sample MR studies and the causal effects of anthropometric traits on breast/prostate cancer would be biased if sex-combined IVs are incorrectly employed.
科研通智能强力驱动
Strongly Powered by AbleSci AI