Department of Biostatistics, Yale University, United States.
School of Statistics and Management, Shanghai University of Finance and Economics, China; Department of Biostatistics, Yale University, United States.
Genomics. 2019 Sep;111(5):1115-1123. doi: 10.1016/j.ygeno.2018.07.006. Epub 2018 Jul 17.
Gene-environment (G-E) interactions have important implications for the etiology and progression of many complex diseases. Compared to continuous markers and categorical disease status, prognosis has been less investigated, with the additional challenges brought by the unique characteristics of survival outcomes. Most of the existing G-E interaction approaches for prognosis data share the limitation that they cannot accommodate long-tailed or contaminated outcomes. In this study, for prognosis data, we develop a robust G-E interaction identification approach using the censored quantile partial correlation (CQPCorr) technique. The proposed approach is built on the quantile regression technique (and hence has a solid statistical basis), uses weights to easily accommodate censoring, and adopts partial correlation to identify important interactions while properly controlling for the main genetic and environmental effects. In simulation, it outperforms multiple competitors with more accurate identification. In the analysis of TCGA data on lung cancer and melanoma, biologically sensible findings different from using the alternatives are made.
基因-环境(G-E)相互作用对许多复杂疾病的病因和进展具有重要意义。与连续标志物和分类疾病状态相比,预后的研究较少,生存结果的独特特征带来了额外的挑战。大多数现有的预后数据 G-E 相互作用方法都存在一个局限性,即它们不能适应长尾或污染的结果。在这项研究中,针对预后数据,我们使用删失分位数部分相关(CQPCorr)技术开发了一种稳健的 G-E 相互作用识别方法。该方法建立在分位数回归技术(因此具有坚实的统计基础)之上,使用权重来轻松适应删失,并采用部分相关来识别重要的相互作用,同时适当控制主要的遗传和环境效应。在模拟中,它比多个竞争对手具有更高的识别准确性。在对肺癌和黑色素瘤 TCGA 数据的分析中,与使用替代方法相比,得出了具有生物学意义的不同发现。