Rava Marta, Smit Lidwien A M, Nadif Rachel
aU1018, Respiratory and Environmental Epidemiology Team, Inserm, Centre for Research in Epidemiology and Population Health (CESP) bUMRS 1018, Université Paris-Sud, Villejuif, Paris, France cDivision of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht, The Netherlands.
Curr Opin Allergy Clin Immunol. 2015 Feb;15(1):70-8. doi: 10.1097/ACI.0000000000000131.
Asthma is a complex disease characterized by an intricate interplay of both heritable and environmental factors. Understanding the mechanisms through which genes and environment interact represents one of the major challenges for pulmonary researchers. This review provides an overview of the recently published literature on gene-environment (G × E) interactions in asthma, with a special focus on the new methodological developments in the postgenomewide association studies (GWAS) era.
Most recent studies on G × E interaction in asthma used a candidate-gene approach. Candidate-gene studies considering exposure to outdoor air pollutants showed significant interactions mainly with variants in the GSTP1 gene on asthma in children. G × E studies on passive and active smoking, including one genomewide interaction study, identified novel genes of susceptibility to asthma and a time-dependent effect of maternal smoking. Other recent studies on asthma found interactions between candidate genes and occupational allergen exposure and several domestic exposures such as endotoxin and gas cooking. New methods were developed to efficiently estimate G × E interaction in GWAS, and a pathway-based strategy to select an enriched gene-set for G × E studies has recently been proposed.
The G × E studies presented in this review offer a good example on how candidate-gene approaches can complement and help in validating GWAS findings.
哮喘是一种复杂疾病,其特征为遗传因素与环境因素之间存在复杂的相互作用。理解基因与环境相互作用的机制是肺部研究人员面临的主要挑战之一。本综述概述了近期发表的关于哮喘基因-环境(G×E)相互作用的文献,特别关注全基因组关联研究(GWAS)时代新的方法学进展。
最近关于哮喘中G×E相互作用的大多数研究采用候选基因方法。考虑接触室外空气污染物的候选基因研究显示,主要与儿童哮喘中GSTP1基因的变异存在显著相互作用。关于被动和主动吸烟的G×E研究,包括一项全基因组相互作用研究,确定了哮喘易感性的新基因以及母亲吸烟的时间依赖性效应。最近其他关于哮喘的研究发现候选基因与职业过敏原暴露以及几种家庭暴露(如内毒素和燃气烹饪)之间存在相互作用。已开发出新方法以有效估计GWAS中的G×E相互作用,并且最近有人提出了一种基于通路的策略来选择用于G×E研究的富集基因集。
本综述中介绍的G×E研究为候选基因方法如何补充和帮助验证GWAS结果提供了一个很好的例子。