A Clinical Service to Support the Return of Secondary Genomic Findings in Human Research

Andrew J Darnell; Howard Austin; David A Bluemke; Richard O Cannon 3rd; Kenneth Fischbeck; William Gahl; David Goldman; Christine Grady; Mark H Greene; Steven M Holland; Sara Chandros Hull; Forbes D Porter; David Resnik; Wendy S Rubinstein; Leslie G Biesecker

doi:10.1016/j.ajhg.2016.01.010

A Clinical Service to Support the Return of Secondary Genomic Findings in Human Research

Am J Hum Genet. 2016 Mar 3;98(3):435-441. doi: 10.1016/j.ajhg.2016.01.010.

Authors

Affiliations

¹ Program in Science and Society, Duke University, Durham, NC 27710, USA.
² Kidney Disease Section, National Institute of Diabetes, Digestive, and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
³ Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD 20892, USA.
⁴ Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood institute, NIH, Bethesda, MD 20892, USA.
⁵ Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
⁶ Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷ Laboratory of Neurogenetics and Office of the Clinical Director, National Institute of Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892, USA.
⁸ Department of Bioethics, Clinical Research Center, NIH, Bethesda, MD 20892, USA.
⁹ Clinical Genetics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
¹⁰ Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20892, USA.
¹¹ Department of Bioethics, Clinical Research Center, NIH, Bethesda, MD 20892, USA; Bioethics Core, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
¹² Section on Molecular Dysmorphology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
¹³ Office of the Director, National Institute of Environmental Health Sciences, NIH, Bethesda, MD 20892, USA.
¹⁴ Information Engineering Branch, National Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20892, USA.
¹⁵ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. Electronic address: leslieb@helix.nih.gov.

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.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Genetic Predisposition to Disease
Genome, Human*
Genomics / methods*
Humans
Incidental Findings*
Sequence Analysis

Grants and funding

Intramural NIH HHS/United States