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Lessons Learned From Past Gene-Environment Interaction Successes

TitleLessons Learned From Past Gene-Environment Interaction Successes
Publication TypeJournal Article
Year of Publication2017
AuthorsRitz, BR, Chatterjee, N, Garcia-Closas, M, Gauderman, WJ, Pierce, BL, Kraft, P, Tanner, CM, Mechanic, LE, McAllister, K
JournalAm J Epidemiol
Volume186
Pagination778-786
Date PublishedOct 01
ISBN Number0002-9262
Accession Number28978190
Keywords*Gene-Environment Interaction, Biomedical Research, Disease/*etiology/genetics, environmental exposure, exposure, gene-environment, Genetic Predisposition to Disease, Genetic Variation, genome-wide association studies, Genome-Wide Association Study/methods, Humans, interactions, metabolism genes, Models, Biological, pathway genes, pharmacogenomics
Abstract

Genetic and environmental factors are both known to contribute to susceptibility to complex diseases. Therefore, the study of gene-environment interaction (GxE) has been a focus of research for several years. In this article, select examples of GxE from the literature are described to highlight different approaches and underlying principles related to the success of these studies. These examples can be broadly categorized as studies of single metabolism genes, genes in complex metabolism pathways, ranges of exposure levels, functional approaches and model systems, and pharmacogenomics. Some studies illustrated the success of studying exposure metabolism for which candidate genes can be identified. Moreover, some GxE successes depended on the availability of high-quality exposure assessment and longitudinal measures, study populations with a wide range of exposure levels, and the inclusion of ethnically and geographically diverse populations. In several examples, large population sizes were required to detect GxEs. Other examples illustrated the impact of accurately defining scale of the interactions (i.e., additive or multiplicative). Last, model systems and functional approaches provided insights into GxE in several examples. Future studies may benefit from these lessons learned.