Pharmacogenetic Discovery in an EMR-Biorepository

Abstract

Adverse drug reactions (ADRs) can be highly influenced by genetic variation. For example, immunosuppressants prescribed to patients who have undergone organ transplantation have severe nephrotoxic side effects. Pharmacogenetic studies aimed at identifying genetic risk factors for ADRs show promise as an important step in their prevention. Biorepositories linked to electronic medical records (EMR), such as Vanderbilt’s BioVU, are an emerging resource for the generation of large datasets to identify genetic variants involved in ADRs. Described in this dissertation is the utilization of BioVU to assess of the performance of Ilumina’s ADME Core Panel, a pharmacogenetic genotyping platform in the research setting. The platform was then applied in BioVU for two research studies. The first study demonstrated the potential of EMR-linked biorepositories to characterize the genetic risk factors for immunosuppressant induced nephrotoxicity. Next, the ADME Core Panel was applied in a phenome-wide association study to identify novel genotype-phenotype associations. An association between a transporter expressed in the proximal tubule of the kidney and renal osteodystrophy was identified.