Abstract
The differential performance of polygenic risk scores (PRSs) by group is one of the major ethical barriers to their clinical use. It is also one of the main practical challenges for any implementation effort. The social repercussions of how people are grouped in PRS research must be considered in communications with research participants, including return of results. Here, we outline the decisions faced and choices made by a large multi-site clinical implementation study returning PRSs to diverse participants in handling this issue of differential performance. Our approach to managing the complexities associated with the differential performance of PRSs serves as a case study that can help future implementers of PRSs to plot an anticipatory course in response to this issue.
Original language | English (US) |
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Pages (from-to) | 999-1005 |
Number of pages | 7 |
Journal | American journal of human genetics |
Volume | 111 |
Issue number | 6 |
DOIs | |
State | Published - Jun 6 2024 |
Funding
The eMERGE Genomic Risk Assessment Network is funded by the National Human Genome Research Institute (NHGRI) through the following grants: U01HG011172 (Cincinnati Children's Hospital Medical Center), U01HG011175 (Children's Hospital of Philadelphia), U01HG008680 (Columbia University), U01HG011176 (Icahn School of Medicine at Mount Sinai), U01HG008685 (Mass General Brigham), U01HG006379 (Mayo Clinic), U01HG011169 (Northwestern University), U01HG011167 (University of Alabama at Birmingham), U01HG008657 (University of Washington), U01HG011181 (Vanderbilt University Medical Center), and U01HG011166 (Vanderbilt University Medical Center serving as the Coordinating Center). We would like to acknowledge members of the Community Coalition for Equity in Research supported by the National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program (UL1TR002541) and Massachusetts Blue Cross Blue Shield for their contributions to this work. The eMERGE Genomic Risk Assessment study was approved by a central institutional review board at Vanderbilt University Medical Center (#211043) and acknowledged by the local institutional review boards under reliance agreements. Informed consent is required from all enrolled individuals. A.C.F.L. owns some stock in Fabric Genomics; E.D.E. is an employee and stockholder of Invitae, advisor and stockholder of Taproot Health, and advisor and stockholder of Exir; R.C.G. receives compensation for advising the following companies: Allelica, Atria, Fabric, Genomic Life, and Juniper Genomics; and is co-founder of Genome Medical and Nurture Genomics; E.E.K. has received personal fees from Regeneron Pharmaceuticals, 23&Me, Allelica, and Illumina; has received research funding from Allelica; and serves on the advisory boards for Encompass Biosciences, Overtone, and Galatea Bio; N.L. received personal fees from Illumina Inc; E.P. is a paid consultant for Allelica Inc.; M.S. is a member of the Institutional Review Board of the All of Us Research Program; J.W.S. is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity), has received grant support from Biogen, Inc. and is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments.
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)