Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot

Julie C Sapp¹, Jennifer J Johnston¹, Kate Driscoll¹, Alexis R Heidlebaugh², Ane Miren Sagardia², D Nadine Dogbe², Kendall L Umstead², Erin Turbitt², Ilias Alevizos³, Jeffrey Baron⁴, Carsten Bönnemann⁵, Brian Brooks⁶, Sandra Donkervoort⁵, Youn Hee Jee⁴, W Marston Linehan⁷, Francis J McMahon⁸, Joel Moss⁹, James C Mullikin¹⁰, Deborah Nielsen⁷, Eileen Pelayo³, Alan T Remaley¹¹, Richard Siegel¹², Helen Su¹³, Carlos Zarate⁸; NISC Comparative Sequencing Program¹⁰; Teri A Manolio¹⁴, Barbara B Biesecker², Leslie G Biesecker¹⁵

Collaborators, Affiliations

Collaborators

Affiliations

¹ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
² Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
³ National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
⁴ Section on Growth Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
⁵ Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurologic Disorders and Stroke, Bethesda, MD 20892, USA.
⁶ Office of the Clinical Director, National Eye Institute, Bethesda, MD 20892, USA.
⁷ Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
⁸ Human Genetics Branch, National Institutes of Mental Health, Bethesda, MD 20892, USA.
⁹ Laboratory of Translational Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
¹⁰ NIH Intramural Sequencing Center, National Human Genome Research Institute, Bethesda, MD 20892, USA.
¹¹ Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
¹² Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
¹³ Human Immunological Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
¹⁴ Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD 20892, USA.
¹⁵ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. Electronic address: lesb@mail.nih.gov.

PMID: 30122538
PMCID: PMC6128311
DOI: 10.1016/j.ajhg.2018.07.018

Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot

Julie C Sapp et al. Am J Hum Genet. 2018.

. 2018 Sep 6;103(3):358-366.

doi: 10.1016/j.ajhg.2018.07.018. Epub 2018 Aug 16.

Authors

Collaborators

Affiliations

¹ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
² Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA.
³ National Institute of Dental and Craniofacial Research, Bethesda, MD 20892, USA.
⁴ Section on Growth Development, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
⁵ Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurologic Disorders and Stroke, Bethesda, MD 20892, USA.
⁶ Office of the Clinical Director, National Eye Institute, Bethesda, MD 20892, USA.
⁷ Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
⁸ Human Genetics Branch, National Institutes of Mental Health, Bethesda, MD 20892, USA.
⁹ Laboratory of Translational Research, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
¹⁰ NIH Intramural Sequencing Center, National Human Genome Research Institute, Bethesda, MD 20892, USA.
¹¹ Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
¹² Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
¹³ Human Immunological Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
¹⁴ Division of Genomic Medicine, National Human Genome Research Institute, Bethesda, MD 20892, USA.
¹⁵ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892, USA. Electronic address: lesb@mail.nih.gov.

PMID: 30122538
PMCID: PMC6128311
DOI: 10.1016/j.ajhg.2018.07.018

Abstract

While consensus regarding the return of secondary genomic findings in the clinical setting has been reached, debate about such findings in the research setting remains. We developed a hybrid, research-clinical translational genomics process for research exome data coupled with a CLIA-validated secondary findings analysis. Eleven intramural investigators from ten institutes at the National Institutes of Health piloted this process. Nearly 1,200 individuals were sequenced and 14 secondary findings were identified in 18 participants. Positive secondary findings were returned by a genetic counselor following a standardized protocol, including referrals for specialty follow-up care for the secondary finding local to the participants. Interviews were undertaken with 13 participants 4 months after receipt of a positive report. These participants reported minimal psychologic distress within a process to assimilate their results. Of the 13, 9 reported accessing the recommended health care services. A sample of 107 participants who received a negative findings report were surveyed 4 months after receiving it. They demonstrated good understanding of the negative secondary findings result and most expressed reassurance (64%) from that report. However, a notable minority (up to 17%) expressed confusion regarding the distinction of primary from secondary findings. This pilot shows it is feasible to couple CLIA-compliant secondary findings to research sequencing with minimal harms. Participants managed the surprise of a secondary finding with most following recommended follow up, yet some with negative findings conflated secondary and primary findings. Additional work is needed to understand barriers to follow-up care and help participants distinguish secondary from primary findings.

Keywords: Mendelian genetic disorders; exome sequencing; incidental findings; psychologic aspects of genetic testing; secondary findings.

Published by Elsevier Inc.

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References

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Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot

Collaborators

Affiliations

Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical