Stanford Mendelian Genomics Research Center

Stanford University, Stanford CA

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY/ABSTRACT The GREGoR Consortium (Genomics Research to Elucidate the Genetics of Rare diseases) is an NHGRI-funded research network that aims to develop and apply approaches to determine the genetic etiology of rare, Mendelian conditions. Specific objectives include: 1) to shift the paradigm of rare disease diagnosis; 2) to develop best practices for clinical translation; and 3) to create a dataset with broad utility. GREGoR seeks to achieve these objectives through the development of new multi-omic technologies including transcriptomic, metabolomic, epigenomic, and proteomic profiles. While GREGoR has been successful in generating multi- omic data, the meaning, interpretation, and clinical implications of these data for individual patients remains complex and uncertain, and currently there are no guidelines for return of Individual Research Results (IRRs) specifically for multi-omics. While existing literature on genomic IRR is informative, it is insufficient to address the many nuanced complexities and additional uncertainties that characterize multi-omic data. With the growing volume of multi-omic research data, there is an urgent need for empirical bioethics research to support development of guidelines for return of multi-omic IRR. Examples of key ethical questions include: How should the validity of multi-omic IRR be determined? How should the risks of returning uncertain information be weighed against potential benefits for participants? In the setting of limited resources, what is the appropriate balance of effort on return of multi-omic IRR with achieving other scientific goals? To address these and other questions, we propose the following Aims: Aim 1: To identify the range of ethical, legal, scientific, and pragmatic challenges to the return of multi-omic IRR to rare disease participants. To achieve this Aim, we will conduct semi-structured interviews with a broad range of stakeholders both within and outside of the GREGoR Consortium, including patient advocates, clinicians, scientists, genetic counselors, legal experts, ethicists, and IRB members. Aim 2: To identify opportunities for the GREGoR Consortium to address key challenges to multi-omic IRR. To achieve this Aim, we will create a draft conceptual map, informed by ongoing Aim 1 interviews and the existing literature on return of genomic IRR, outlining challenges to return of multi-omics IRR. We will then convene a facilitated workshop, in conjunction with an existing GREGoR in-person meeting, to discuss approaches with GREGoR leaders, collaboratively elicit individuals’ perspectives on potential solutions, and identify opportunities for GREGoR address these challenges. The long-term goal of this research is to develop and refine ethical and policy guidelines related to return of multi- omic IRR and clinical translation of new multi-omic technologies.