Gene-environment-wide association studies_emerging approaches英文版本.pdf

R E V I E W S G e n o m e - w i d e a s s o c i at i o n s t u d i e s Gene–environment-wide association studies: emerging approaches Duncan Thomas Abstract | 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. Marginal effects The term ‘interaction’ has various meanings in the of G×E interactions in risk prediction models can have The effects of a specific risk epidemiologic literature, depending on the context (BOX 1). important implications for both public health and factor (gene or exposure) 7