Gene--environment-wide association studies: emerging approaches

Nat Rev Genet. 2010 Apr;11(4):259-72. doi: 10.1038/nrg2764.


Despite the yield of recent genome-wide association (GWA) studies, the identified variants explain only a small proportion of the heritability of most complex diseases. This unexplained heritability could be partly due to gene--environment (G×E) interactions or more complex pathways involving multiple genes and exposures. This Review provides a tutorial on the available epidemiological designs and statistical analysis approaches for studying specific G×E interactions and choosing the most appropriate methods. I discuss the approaches that are being developed for studying entire pathways and available techniques for mining interactions in GWA data. I also explore methods for marrying hypothesis-driven pathway-based approaches with 'agnostic' GWA studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Review
  • Validation Study

MeSH terms

  • Data Mining
  • Environment*
  • Epigenesis, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Genome-Wide Association Study / statistics & numerical data
  • Genome-Wide Association Study / trends
  • Humans
  • Models, Genetic
  • Risk Factors