title: A Clinical Service to Support the Return of Secondary Genomic Findings in Human Research.
abstract: Human genome and exome sequencing are powerful research tools that can generate secondary findings beyond the scope of the research. Most secondary genomic findings are of low importance, but some (for a current estimate of 1%-3% of individuals) confer high risk of a serious disease that could be mitigated by timely medical intervention. The impact and scope of secondary findings in genome and exome sequencing will only increase in the future. There is considerable agreement that high-impact findings should be returned to participants, but many researchers performing genomic research studies do not have the background, skills, or resources to identify, verify, interpret, and return such variants. Here, we introduce a proposal for the formation of a secondary-genomic-findings service (SGFS) that would support researchers by enabling the return of clinically actionable sequencing results to research participants in a standardized manner. We describe a proposed structure for such a centralized service and evaluate the advantages and challenges of the approach. We suggest that such a service would be of greater benefit to all parties involved than present practice, which is highly variable. We encourage research centers to consider the adoption of a centralized SGFS.
authors.affiliation: Program in Science and Society, Duke University, Durham, NC 27710, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Darnell
authors.affiliation: Kidney Disease Section, National Institute of Diabetes, Digestive, and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Austin
authors.affiliation: Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD 20892, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Richard O
authors.initials: RO
authors.lastname: Cannon
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fischbeck
authors.affiliation: Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: William
authors.initials: W
authors.lastname: Gahl
authors.affiliation: Laboratory of Neurogenetics and Office of the Clinical Director, National Institute of Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Department of Bioethics, Clinical Research Center, NIH, Bethesda, MD 20892, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Grady
authors.affiliation: Clinical Genetics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20892, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.affiliation: Department of Bioethics, Clinical Research Center, NIH, Bethesda, MD 20892, USA; Bioethics Core, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Sara Chandros
authors.initials: SC
authors.lastname: Hull
authors.affiliation: Section on Molecular Dysmorphology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
authors.affiliation: Office of the Director, National Institute of Environmental Health Sciences, NIH, Bethesda, MD 20892, USA.
authors.forename: David
authors.initials: D
authors.lastname: Resnik
authors.affiliation: Information Engineering Branch, National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20892, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Rubinstein
authors.affiliation: Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. Electronic address: leslieb@helix.nih.gov.
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Biesecker
mesh_terms: D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D033162:Incidental Findings; D017421:Sequence Analysis