Pérusse Louis, Jacob Raphaëlle, Drapeau Vicky, Llewellyn Clare, Arsenault Benoit J, Bureau Alexandre, Labonté Marie-Ève, Tremblay Angelo, Vohl Marie-Claude
Department of Kinesiology, Faculty of Medicine, Université Laval, Québec, Québec, Canada.
Centre Nutrition, Santé et Société (NUTRISS), Institute of Nutrition and Functional Foods (INAF), Québec, Québec, Canada.
Lifestyle Genom. 2022;15(2):67-76. doi: 10.1159/000523813. Epub 2022 Mar 1.
Obesity results from complex interactions between genetic susceptibility to weight gain and poor eating and lifestyle behaviors. The approach that has been traditionally used in genetics to investigate gene-environment/lifestyle interaction in obesity is based on the concept of moderation or effect modification. Another approach called mediation analysis can be used to investigate gene-environment interaction in obesity. The objective of this review article is to explain the differences between the concepts of moderation and mediation and summarize the studies that have used mediation analysis to support the role of eating or lifestyle behaviors as putative mediators of genetic susceptibility to obesity.
Moderation is used to determine whether the effect of an exposure (genes associated with obesity) on an outcome (obesity phenotype) differs in magnitude and/or direction across the spectrum of environmental exposure. Mediation analysis is used to assess the extent to which the effect of the exposure on the outcome is explained by a given set of hypothesized mediators with the aim of understanding how the exposure could lead to the outcome. In comparison with moderation, relatively few studies used mediation analyses to investigate gene-environment interaction in obesity. Most studies found evidence that traits related to appetite or eating behaviors partly mediated genetic susceptibility to obesity in either children or adults.
Moderation and mediation represent two complementary approaches to investigate gene-environment interaction in obesity and address different research questions pertaining to the cause-effect relationship between genetic susceptibility to obesity and various obesity outcomes. More studies relying on mediation are needed to better understand the role of eating and lifestyle habits in mediating genetic susceptibility to obesity.
肥胖是由体重增加的遗传易感性与不良饮食及生活方式行为之间复杂的相互作用导致的。遗传学中传统上用于研究肥胖中基因-环境/生活方式相互作用的方法基于调节或效应修正的概念。另一种称为中介分析的方法可用于研究肥胖中的基因-环境相互作用。本文综述的目的是解释调节和中介概念之间的差异，并总结那些使用中介分析来支持饮食或生活方式行为作为肥胖遗传易感性推定中介作用的研究。
调节用于确定暴露因素（与肥胖相关的基因）对结局（肥胖表型）的影响在整个环境暴露范围内在大小和/或方向上是否不同。中介分析用于评估暴露因素对结局的影响在多大程度上由一组给定的假设中介因素所解释，目的是了解暴露因素如何导致结局。与调节相比，相对较少的研究使用中介分析来研究肥胖中的基因-环境相互作用。大多数研究发现，与食欲或饮食行为相关的特征在一定程度上介导了儿童或成人肥胖的遗传易感性。
调节和中介是研究肥胖中基因-环境相互作用的两种互补方法，解决了与肥胖遗传易感性和各种肥胖结局之间因果关系相关的不同研究问题。需要更多依赖中介分析的研究来更好地理解饮食和生活习惯在介导肥胖遗传易感性中的作用。
