International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review.

Autor:	Majeed S; Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada., Johnston C; Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada., Saeedi S; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Mighton C; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Rokoszak V; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Abbasi I; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Grewal S; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Aguda V; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada., Kissoondoyal A; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada., Malkin D; Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Division of Hematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada., Bombard Y; Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada; Genetics Adviser, Toronto, ON, Canada. Electronic address: yvonne.bombard@utoronto.ca.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2024 Oct 03; Vol. 111 (10), pp. 2079-2093. Date of Electronic Publication: 2024 Sep 18.
DOI:	10.1016/j.ajhg.2024.08.012
Abstrakt:	Secondary findings (SFs) from genomic sequencing can have significant impacts on patient health, yet existing practices guiding their clinical investigation are inconsistent. We systematically reviewed existing SFs policies to identify variations and gaps in guidance. We cataloged and appraised international policies from academic databases (n = 5, inception-02/2022) and international human genetic societies (n = 64; inception-05/2022), across the continuum of SFs selection, analysis, and clinical management. We assessed quality using AGREE-II and interpreted results using qualitative description. Of the 63 SFs policies identified, most pertained to clinical management of SFs (98%; n = 62; primarily consent and disclosure), some guided SFs analysis (60%; n = 38), while fewer mentioned SFs selection (48%; n = 30). Overall, policies recommend (1) identifying clinically actionable, pathogenic variants with high positive predictive values for disease (selection), (2) bioinformatically filtering variants using evidence-informed gene lists (analysis), and (3) discussing with affected individuals the SFs identified, their penetrance, expressivity, medical implications, and management (clinical management). Best practices for SFs variant analysis, clinical validation, and follow-up (i.e., surveillance, treatment, etc.) were minimally described. Upon quality assessment, policies were highly rated for scope and clarity (median score, 69) but were limited by their rigor and applicability (median scores, 27 and 25). Our review represents a comprehensive international synthesis of policy guiding SFs across the continuum of selection, analysis, and clinical management. Our synthesis will help providers navigate critical decision points in SFs investigation, although significant work is needed to address gaps in SFs analysis, clinical validation, and follow-up processes and to support evidence-based practice. Competing Interests: Declaration of interests Y.B. is a co-author of one of the guidelines included in this review and a member of the Board of Directors of ASHG. (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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