Phenome-wide association study (PheWAS) is a reverse genetic analysis method to identify the potential phenotypes associated with genetic variations. With the increasing availability of biomedical databases and electronic medical records (EMR), PheWAS has gradually become an effective tool to unveil the relationships between exposure and a broad range of health phenotypes. The unique advantage of this method is that it can simultaneously explore the associations of a specific exposure with a variety of disease outcomes, thus helping to reveal multiple causal relationships and the shared pathogenic mechanisms among diseases. However, PheWAS has limitations, including selecting instrumental variables and the heavy burden of various corrections. In addition, how to interpret the biological mechanisms underlying significant findings is another crucial issue of PheWAS. This review will focus on the methodology and application of PheWAS to provide meaningful suggestions and insights for future studies.

Phenome-wide association study; Biomedical big data; Electronic medical records; Pleiotropy