Cancers are known for the racial disparities in terms of germline mutations, type of somatic driver mutations, distribution of histology subtypes, and association with one another across cancer types. Epidemiology studies have demonstrated increased risks of second primary cancers for cancer survivors, which cannot be solely attributed to the shared risk factors, such as smoking behavior or chemo-radiation exposure. Importantly, these associations vary within and across racial populations and geographic areas, highlighting the contribution of the interactions between genetic background, life style, and environmental exposure.
Moreover, the response to cancer treatment also varies among individuals within and across racial groups. Studies have shown that the crosstalks between germline alterations, somatic mutations, and epigenetic modifications constitute distinct genotypes as well as immunophenotypes, which play significant roles in the differential responses to the treatment.
Furthermore, diseases other than cancer, such as autoimmune and metabolic diseases, also show racial disparities in terms of age at disease onset, clinical phenotypes, responses to treatment, and disease outcomes. Likewise, lines of evidence suggested the roles of genome-phenome interactions in these clinical characteristics.
In this proposal, we aim to characterize the roles of genome-phenome interactions in disease susceptibility, treatment responses, and disease outcomes in several major disease entities, such as the cancer, autoimmune, metabolic, cardiovascular, and infectious diseases. The phenome data used for analysis include the de-identified electronic medical records, questionnaires, laboratory test results, metabolomics results, and image data. The genome data used for analysis include the genotyping as well as the whole genome and whole exome sequencing data.