Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study

M Ragan Hart; Barbara B Biesecker; Carrie L Blout; Kurt D Christensen; Laura M Amendola; Katie L Bergstrom; Sawona Biswas; Kevin M Bowling; Kyle B Brothers; Laura K Conlin; Greg M Cooper; Matthew C Dulik; Kelly M East; Jessica N Everett; Candice R Finnila; Arezou A Ghazani; Marian J Gilmore; Katrina A B Goddard; Gail P Jarvik; Jennifer J Johnston; Tia L Kauffman; Whitley V Kelley; Joel B Krier; Katie L Lewis; Amy L McGuire; Carmit McMullen; Jeffrey Ou; Sharon E Plon; Heidi L Rehm; C Sue Richards; Edward J Romasko; Ane Miren Sagardia; Nancy B Spinner; Michelle L Thompson; Erin Turbitt; Jason L Vassy; Benjamin S Wilfond; David L Veenstra; Jonathan S Berg; Robert C Green; Leslie G Biesecker; Lucia A Hindorff

doi:10.1038/s41436-018-0308-x

Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study

Genet Med. 2019 May;21(5):1100-1110. doi: 10.1038/s41436-018-0308-x. Epub 2018 Oct 5.

Authors

M Ragan Hart^{1

2}, Barbara B Biesecker³, Carrie L Blout⁴, Kurt D Christensen^{4

5}, Laura M Amendola^{6

7}, Katie L Bergstrom⁸, Sawona Biswas⁹, Kevin M Bowling¹⁰, Kyle B Brothers¹¹, Laura K Conlin^{12

13}, Greg M Cooper¹⁰, Matthew C Dulik^{12

13}, Kelly M East¹⁰, Jessica N Everett^{14

15}, Candice R Finnila¹⁰, Arezou A Ghazani¹⁶, Marian J Gilmore¹⁷, Katrina A B Goddard¹⁸, Gail P Jarvik^{6

7}, Jennifer J Johnston¹⁹, Tia L Kauffman¹⁸, Whitley V Kelley¹⁰, Joel B Krier⁴, Katie L Lewis¹⁹, Amy L McGuire²⁰, Carmit McMullen¹⁸, Jeffrey Ou⁷, Sharon E Plon⁸, Heidi L Rehm^{5

21

22}, C Sue Richards²³, Edward J Romasko¹², Ane Miren Sagardia³, Nancy B Spinner¹², Michelle L Thompson¹⁰, Erin Turbitt³, Jason L Vassy^{4

5

24}, Benjamin S Wilfond²⁵, David L Veenstra^#^{7

26}, Jonathan S Berg^#²⁷, Robert C Green^#^{4

5

22

28}, Leslie G Biesecker^#¹⁹, Lucia A Hindorff^#²⁹

Affiliations

¹ Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA. hartmr@uw.edu.
² Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA. hartmr@uw.edu.
³ Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
⁴ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁵ Harvard Medical School, Boston, MA, USA.
⁶ Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA.
⁷ Clinical Sequencing Exploratory Research Coordinating Center, University of Washington, Seattle, WA, USA.
⁸ Department of Pediatrics, Oncology Section, Baylor College of Medicine, Houston, TX, USA.
⁹ Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁰ HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
¹¹ Department of Pediatrics, University of Louisville, Louisville, KY, USA.
¹² Division of Genomic Diagnostics, Department of Pathology and Laboratory Medicine, The Children's Hospital, Philadelphia, PA, USA.
¹³ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
¹⁵ Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
¹⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁷ Department of Medical Genetics, Kaiser Permanente Northwest, Portland, OR, USA.
¹⁸ Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA.
¹⁹ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
²⁰ Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX, USA.
²¹ Laboratory for Molecular Medicine, Partners HealthCare, Cambridge, MA, USA.
²² Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²³ Knight Diagnostic Laboratories, Oregon Health Science University, Portland, OR, USA.
²⁴ VA Boston Healthcare System, Boston, MA, USA.
²⁵ Department of Pediatrics and Seattle Children's Research Institute, University of Washington, Seattle, WA, USA.
²⁶ Department of Pharmacy, University of Washington, Seattle, WA, USA.
²⁷ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²⁸ Partners Personalized Medicine, Boston, MA, USA.
²⁹ Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. hindorffl@mail.nih.gov.

^# Contributed equally.

Abstract

Purpose: Clinical sequencing emerging in health care may result in secondary findings (SFs).

Methods: Seventy-four of 6240 (1.2%) participants who underwent genome or exome sequencing through the Clinical Sequencing Exploratory Research (CSER) Consortium received one or more SFs from the original American College of Medical Genetics and Genomics (ACMG) recommended 56 gene-condition pair list; we assessed clinical and psychosocial actions.

Results: The overall adjusted prevalence of SFs in the ACMG 56 genes across the CSER consortium was 1.7%. Initially 32% of the family histories were positive, and post disclosure, this increased to 48%. The average cost of follow-up medical actions per finding up to a 1-year period was $128 (observed, range: $0-$678) and $421 (recommended, range: $141-$1114). Case reports revealed variability in the frequency of and follow-up on medical recommendations patients received associated with each SF gene-condition pair. Participants did not report adverse psychosocial impact associated with receiving SFs; this was corroborated by 18 participant (or parent) interviews. All interviewed participants shared findings with relatives and reported that relatives did not pursue additional testing or care.

Conclusion: Our results suggest that disclosure of SFs shows little to no adverse impact on participants and adds only modestly to near-term health-care costs; additional studies are needed to confirm these findings.

Keywords: genomic sequencing; health-care resource utilization; secondary findings.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Decision Making / ethics
Disclosure
Exome
Female
Genetic Testing / economics*
Genetic Testing / ethics
Genetic Testing / standards
Genomics / methods
Health Care Costs
Health Knowledge, Attitudes, Practice
Health Personnel
High-Throughput Nucleotide Sequencing / ethics
Humans
Incidental Findings*
Intention
Male
Patients
Prevalence
Whole Genome Sequencing / economics
Whole Genome Sequencing / ethics*

Abstract

Publication types

MeSH terms

Grants and funding