Project Summary

The informatics work on this project centers on the integration of whole exome sequence data into the Electronic Health Record. Subprojects include a) working on and with variant annotation databases, b) integrating reports on exome sequencing into the EHR, and c) integrating computable variant data into the EHR for automated decision support with an emphasis on pharmacogenomics and ACMG panel testing.

The overall project is part of NHGRI Clinical Sequencing and Exploratory Research (CSER) initiative. The overall project proposes a randomized controlled trial of usual care vs. the addition of exome analysis in University of Washington Medical Genetics Clinic patients who have clinical indications for colorectal cancer/polyposis (CRCP) genetic testing. We will evaluate the effectiveness of this technology for the identification of clinically relevant CRCP gene mutations, cost, and patient derived measures. After deliberations by experts to indentify variants that are incidental findings that should be returned, we will also return CLIA certified results to the participants. We will obtain structured feedback from subjects in both the usual care and exome arms of the RCT to evaluate their experiences. We will further consider the input of referring physicians and patients using focus groups. We will investigate the legal basis of the need to return CLIA certified research results. An important component of our work is determination of not only which results to return, but how best to incorporate these genomic data into the medical record. Finally, we will perform CRCP gene discovery studies for families without identifiable CRCP mutations; such novel gene discovery can impact prevention and treatment.