Research on “candidate environmental risks” can be combined with theory-free genetics to discover novel loci in two ways. One way is to turn GWAS into Gene-Environment-Wide Interaction Studies (137). Theoretically, the ability to measure G×E interactions should sharpen measurement of gene-disease associations in subsets of the population and even potentially increase statistical power to detect such associations (137). This will become increasingly possible as researchers seek to integrate genome-wide information with information about environmental exposures gathered in the context of epidemiological studies. But sample sizes will become prohibitive when testing gene-environment-wide interactions because 1) more tests are involved, 2) tests for interactions have less power compared to tests for main effects, and 3) environmental exposures introduce additional measurement error. If genetic epidemiologists embrace purely agnostic, theory-free approaches and data-mining tools in studying G×E interactions, the “fishing expedition” may net little. The new generation of purpose-built Gene-Environment-Wide Interaction studies may be an improvement over opportunistic studies published in these early years of G×E research, but even these will fall short unless they attend to the measurement of environmental exposures. An alternative
