Wu Mengyun, Li Yingmeng, Ma Shuangge
School of Statistics and Management, Shanghai University of Finance and Economics, Shanghai, China.
Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA.
Annu Rev Stat Appl. 2025 Mar;12. doi: 10.1146/annurev-statistics-112723-034315. Epub 2024 Sep 11.
Beyond the main genetic and environmental effects, gene-environment (G-E) interactions have been demonstrated to significantly contribute to the development and progression of complex diseases. Published analyses of G-E interactions have primarily used a supervised framework to model both low-dimensional environmental factors and high-dimensional genetic factors in relation to disease outcomes. In this article, we aim to provide a selective review of methodological developments in G-E interaction analysis from a statistical perspective. The three main families of techniques are hypothesis testing, variable selection, and dimension reduction, which lead to three general frameworks: testing-based, estimation-based, and prediction-based. Linear- and nonlinear-effects analysis, fixed- and random-effects analysis, marginal and joint analysis, and Bayesian and frequentist analysis are reviewed to facilitate the conduct of interaction analysis in a wide range of situations with various assumptions and objectives. Statistical properties, computations, applications, and future directions are also discussed.
除了主要的遗传和环境影响外,基因-环境(G-E)相互作用已被证明对复杂疾病的发生和发展有显著贡献。已发表的G-E相互作用分析主要使用监督框架来对与疾病结局相关的低维环境因素和高维遗传因素进行建模。在本文中,我们旨在从统计学角度对G-E相互作用分析方法的发展进行选择性综述。主要的三类技术是假设检验、变量选择和降维,这导致了三个通用框架:基于检验的、基于估计的和基于预测的。本文回顾了线性和非线性效应分析、固定和随机效应分析、边际和联合分析以及贝叶斯和频率论分析,以促进在具有各种假设和目标的广泛情况下进行相互作用分析。还讨论了统计特性、计算方法、应用以及未来方向。