Systems genetics: a powerful approach for gene-environment interactions.

Genetic variation in a population creates an impressive spectrum of phenotypic diversity, particularly when changes in diet or the environment are imposed on the population. Genome-wide association studies have become a powerful tool for linking sequence variants with overlying systems level phenotypes, but they do not provide insight into the mechanisms through which genetic variation drives phenotypic variation. Systems genetics is an emerging discipline that provides a means to fill this knowledge gap by assembling the hierarchy of interactions among genes, proteins, and other intermediate phenotypes that manifest as phenotypic variation. When applied to nutrition, systems genetics enables the identification of pathways through which nutrients influence health and the determination of the mechanisms that cause individuals to differ in their response to diet.