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American Journal of Epidemiology Advance Access published online on November 20, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn351
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Invited Commentary: From Genome-Wide Association Studies to Gene-Environment-Wide Interaction Studies—Challenges and Opportunities

Muin J. Khoury and Sholom Wacholder

Correspondence to Dr. Muin J. Khoury, National Office of Public Health Genomics, Centers for Disease Control and Prevention, 4770 Buford Highway, MS K-89, Atlanta, GA 30341 (e-mail: muk1{at}cdc.gov).

Received for publication May 30, 2008. Accepted for publication July 25, 2008.

The recent success of genome-wide association studies in finding susceptibility genes for many common diseases presents tremendous opportunities for epidemiologic studies of environmental risk factors. Analysis of gene-environment interactions, included in only a small fraction of epidemiologic studies until now, will begin to accelerate as investigators integrate analyses of genome-wide variation and environmental factors. Nevertheless, considerable methodological challenges are involved in the design and analysis of gene-environment interaction studies. The authors review these issues in the context of evolving methods for assessing interactions and discuss how the current agnostic approach to interrogating the human genome for genetic risk factors could be extended into a similar approach to gene-environment-wide interaction studies of disease occurrence in human populations.

environment; epidemiologic methods; genetics; genomics

Abbreviations: GEWIS, gene-environment-wide interaction studies; GWAS, genome-wide association studies; HuGE, human genome epidemiology


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