Journal
NATURE REVIEWS GENETICS
Volume 11, Issue 4, Pages 259-272Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrg2764
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Funding
- US National Institute of Environmental Health Sciences [5P30 ES007043, 1U01 ES15090, 1R01 ES016813]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [T32ES007043, R01ES016813, U01ES015090, P30ES007048, R01ES019876] Funding Source: NIH RePORTER
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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 x 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 x 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.
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