Study design and analysis considerations in genome-wide studies of gene-environment interactions

Most complex human diseases are believed to be influenced by a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in the development of complex diseases and disease prognosis. Numerous candidate gene studies to investigate specific gene-environment interactions have been performed, and hypothesis-generating genome-wide gene-environment interaction studies are beginning to emerge. This chapter provides an overview of study designs, various analytical approaches for studying gene-environment interactions, and potential sources of biases. Powerful statistical approaches suitable for genome-wide analyses, including two-step filtering approaches, data-mining methods, and gene-level and pathway-level analyses are also discussed.