Background: Mediation analysis is emerging as an alternative approach to moderation to investigate gene-diet interaction in obesity and to identify nutritional mediators of genetic susceptibility to obesity.
Objective: The objective of this presentation is to explain the differences between the concepts of mediation and moderation and provide an overview of recent studies that have used mediation analysis to support the role of eating and lifestyle behaviors in mediating genetic susceptibility to obesity.
Content: Moderation analysis is used to investigate the role of nutrition/lifestyle in modifying the association between genetic susceptibility to obesity and an obesity-related trait, while mediation analysis is used to identify nutrition/lifestyle factors explaining how genetic susceptibility to obesity exerts its effect on an obesity outcome. Using data from the Quebec Family Study, we have recently shown that eating behaviors, diet quality and intake of specific food groups partly mediated the association between genetic susceptibility to obesity and body mass index.
Conclusion: Moderation and mediation analyses represent two complementary approaches to investigate gene-diet interaction in obesity or the cause-effect relationship between genetic susceptibility to obesity and various obesity outcomes. Future studies relying on mediation will contribute to improve our understanding of the role of nutrition in explaining how genetic susceptibility to obesity impacts body weight or other obesity-related traits, which will offer new opportunities for precision nutrition initiatives aimed at the prevention and treatment of obesity.
Dr Louis Pérusse is Professor in the Department of Kinesiology at the Faculty of Medicine in Laval University, Québec. He is a genetic epidemiologist with more than 30 years of research experience in the field of the genetics of complex diseases such as obesity, diabetes and cardiovascular diseases. Dr Pérusse is a member of the Nutrition Santé et Société (NUTRISS) Research Center at the Institute of Nutrition Functional Foods (INAF) of Laval University and President of the International Society of Nutrigenetics and Nutrigenomics (ISNN). He is the author of more than 400 papers and 250 communications in the field of genetics of obesity and its related-metabolic complications and of adaptation to exercise training.