Appraisal of Gene-Environment Interactions in GWAS for Evidence-Based Precision Nutrition Implementation

Abstract

Purpose of Review This review aims to analyse the currently reported gene-environment (G × E) interactions in genome-wide association studies (GWAS), involving environmental factors such as lifestyle and dietary habits related to metabolic syndrome phenotypes. For this purpose, the present manuscript reviews the available GWAS registered on the GWAS Catalog reporting the interaction between environmental factors and metabolic syndrome traits. Recent Findings Advances in omics-related analytical and computational approaches in recent years have led to a better understanding of the biological processes underlying these G × E interactions. A total of 42 GWAS were analysed, reporting over 300 loci interacting with environmental factors. Alcohol consumption, sleep time, smoking habit and physical activity were the most studied environmental factors with significant G × E interactions. Summary The implementation of more comprehensive GWAS will provide a better understanding of the metabolic processes that determine individual responses to environmental exposures and their association with the development of chronic diseases such as obesity and the metabolic syndrome. This will facilitate the development of precision approaches for better prevention, management and treatment of these diseases.

Heuristic Approach Uncovering Biological Significance of Gene-Lifestyle Interactions in Cardiometabolic Traits

“…In this regard, some authors are developing Mendelian randomization analyses using summary data from GWAS as a novel assessment of causality in genetic studies [12]. Despite the change in trend in recent years, with the inclusion of new populations and multi-ethnic populations in GWAS studies, the majority of studies are still conducted on population of European origin [4]. This may provide greater robustness to the applicability of the results due to the homogeneity of the populations in these heuristic analyses.…”

“…Table 1; for all online suppl. material, see https://doi.org/10.1159/000531181) exhibiting interactions between cardiometabolic traits and lifestyle factors [4] were extracted from the GWAS Catalog (https://www.ebi.ac.uk/gwas/) [5] using the gwasrapidd R package [6]. Lifestyle factors were defined as modifiable habits that can influence cardiometabolic health, including nutritional and dietary intake, physical activity, smoking, and sleep habits.…”

“…Lifestyle factors were defined as modifiable habits that can influence cardiometabolic health, including nutritional and dietary intake, physical activity, smoking, and sleep habits. The complete list of terms used for searching GWAS datasets can be found in the online supplementary material of our previous review [4]. A total of 873 mapped genes containing polymorphisms with a significant interaction record were collected to perform a heuristic analysis procedure, as shown in Figure 1.…”

“…This may help nutritionist/ practitioners classify individuals according to their risk and predict the response to a modification of lifestyle habits. For this purpose, the identification of genetic variants showing interactions with environmental or behavioral components, and sharing biological pathways, may facilitate the integration of this knowledge into clinical practice guidelines [4]. The present report aimed at performing a heuristic analysis of the current reported overlapping genes interacting with environmental and lifestyle factors to provide a better understanding of the biological significance of genelifestyle interactions in the development of cardiometabolic diseases.…”

Frequency of Consumption of Food Groups and Cardio-Metabolic Risk Factors: A Genetically Informative Twin Study in Sri Lanka

“…Considering combined effects of multiple genes, a significant interaction effect between the genetic cardiometabolic risk score and a low-protein diet on BMI, waist circumference, and triglyceride levels among Southeast Asian women was reported (Alsulami et al 2020 ). A comprehensive review of the evidence of 42 Genome Wide Association Studies (GWAS) reporting G × E interactions of lifestyle and dietary habits related to metabolic syndrome was recently published (San-Cristobal et al 2022 ). Inclusion of the interaction terms in constructing genetic risk scores to increase their predictive power was proposed.…”