Phenome-wide association study maps genetic variation in epigenetic factors with human complex diseases. Homo sapiens

Human complex disease is generated by the interaction between genetics, epigenetics and environment. While the rationale for genetic association studies have been supported by different fundamental observations such as heritability estimation from twin studies, there is no fundamental research to illustrate whether epigenetic changes are involved in disease phenotypes, although we know that epigenetic elements are an importance interface between the interaction of genetics and environment. In this study, I hypothesize that genetic variants in epigenetic genes are a proxy to infer the epigenetic involvement in phenotypes. In this study, we will apply a phenome-wide association study (PheWAS) approach to test the association between a panel of epigenetic factors against 6,221 clinical traits within the Marshfield Clinic Personalized Medicine Research Project (PMRP) dataset. This will enable us to identify all the significant phenotypes whose pathology are potentially driven by epigenetic changes and apply the measurement of genome-wide DNA methylation levels in the corresponding phenotypes to validate the above findings.