Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience

The members of the CSER Actionability and Return of Results Working Group

doi:10.1002/mgg3.453

Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience

The members of the CSER Actionability and Return of Results Working Group

Academics (Law)

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Background: Clinical genome and exome sequencing (CGES) is primarily used to address specific clinical concerns by detecting risk of future disease, clarifying diagnosis, or directing treatment. Additionally, CGES makes possible the disclosure of autosomal recessive and X-linked carrier results as additional secondary findings, and research about the impact of carrier results disclosure in this context is needed. Methods: Representatives from 11 projects in the clinical sequencing exploratory research (CSER) consortium collected data from their projects using a structured survey. The survey focused on project characteristics, which variants were offered and/or disclosed to participants as carrier results, methods for carrier results disclosure, and project-specific outcomes. We recorded quantitative responses and report descriptive statistics with the aim of describing the variability in approaches to disclosing carrier results in translational genomics research projects. Results: The proportion of participants with carrier results was related to the number of genes included, ranging from 3% (three genes) to 92% (4,600 genes). Between one and seven results were disclosed to those participants who received any positive result. Most projects offered participants choices about whether to receive some or all of the carrier results. There were a range of approaches to communicate results, and many projects used separate approaches for disclosing positive and negative results. Conclusion: Future translational genomics research projects will need to make decisions regarding whether and how to disclose carrier results. The CSER consortium experience identifies approaches that balance potential participant interest while limiting impact on project resources.

Original language	English (US)
Pages (from-to)	898-909
Number of pages	12
Journal	Molecular Genetics and Genomic Medicine
Volume	6
Issue number	6
DOIs	https://doi.org/10.1002/mgg3.453
State	Published - Nov 2018

Bibliographical note

Funding Information:
National Human Genome Research Institute, Grant/Award Number: R01 CA154517, R01 HG006600, R01 HG006618, R01 HG008605, U01 HG006485, U01 HG006487, U01 HG006492, U01 HG006500, U01 HG006507, U01 HG006546, U01 HG007307, UM1 HG007301, UM1 HG007292; Intramural Research Program of the National Human Genome Research Institute, Grant/Award Number: ZIA HG20038703

Funding Information:
The authors thank all of the clinical sequencing exploratory research (CSER) staff and participants for their support and involvement in this research. This work was supported by grants from the National Human Genome Research Institute and National Cancer Institute (U01 HG006485, MPI: Plon, Parsons; U01 HG006500, PI: Green; U01 HG006546, MPI: Krantz, Spinner; U01 HG006492, MPI: van Allen, Janne; UM1 HG007301, MPI: Myers, Cooper; UM1 HG007292, MPI: Goddard, Wilfond; U01 HG006487, MPI: Evans, Berg, Henderson; U01 HG006507, PI: Jarvik; R01 HG006600, PI: Chung; R01 HG006618, PI: Tabor; R01 CA154517, MPI: Petersen, Koenig, Wolf; R01 HG008605, MPI: Wolf, Clayton, Lawrenz; with additional support from U01 HG007307 (Coordinating Center)) as part of the clinical sequencing exploratory research (CSER) consortium. The ClinSeq project was supported by the Intramural Research Program of the National Human Genome Research Institute (ZIA HG20038703, PI: Biesecker).

Publisher Copyright:
© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Keywords

carrier testing
exome
genome
secondary findings
translational genomics research

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Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience. / The members of the CSER Actionability and Return of Results Working Group.
In: Molecular Genetics and Genomic Medicine, Vol. 6, No. 6, 11.2018, p. 898-909.

Research output: Contribution to journal › Article › peer-review

@article{f197afc17cab46eeb22fcc313e27dcf1,

title = "Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience",

abstract = "Background: Clinical genome and exome sequencing (CGES) is primarily used to address specific clinical concerns by detecting risk of future disease, clarifying diagnosis, or directing treatment. Additionally, CGES makes possible the disclosure of autosomal recessive and X-linked carrier results as additional secondary findings, and research about the impact of carrier results disclosure in this context is needed. Methods: Representatives from 11 projects in the clinical sequencing exploratory research (CSER) consortium collected data from their projects using a structured survey. The survey focused on project characteristics, which variants were offered and/or disclosed to participants as carrier results, methods for carrier results disclosure, and project-specific outcomes. We recorded quantitative responses and report descriptive statistics with the aim of describing the variability in approaches to disclosing carrier results in translational genomics research projects. Results: The proportion of participants with carrier results was related to the number of genes included, ranging from 3% (three genes) to 92% (4,600 genes). Between one and seven results were disclosed to those participants who received any positive result. Most projects offered participants choices about whether to receive some or all of the carrier results. There were a range of approaches to communicate results, and many projects used separate approaches for disclosing positive and negative results. Conclusion: Future translational genomics research projects will need to make decisions regarding whether and how to disclose carrier results. The CSER consortium experience identifies approaches that balance potential participant interest while limiting impact on project resources.",

keywords = "carrier testing, exome, genome, secondary findings, translational genomics research",

author = "{The members of the CSER Actionability and Return of Results Working Group} and Porter, {Kathryn M.} and Kauffman, {Tia L.} and Koenig, {Barbara A.} and Lewis, {Katie L.} and Rehm, {Heidi L.} and Richards, {Carolyn Sue} and Strande, {Natasha T.} and Tabor, {Holly K.} and Wolf, {Susan M.} and Yaping Yang and Amendola, {Laura M.} and Azzariti, {Danielle R.} and Berg, {Jonathan S.} and Katie Bergstrom and Biesecker, {Leslie G.} and Sawona Biswas and Bowling, {Kevin M.} and Chung, {Wendy K.} and Clayton, {Ellen W.} and Conlin, {Laura K.} and Cooper, {Gregory M.} and Dulik, {Matthew C.} and Garraway, {Levi A.} and Ghazani, {Arezou A.} and Green, {Robert C.} and Hiatt, {Susan M.} and Jamal, {Seema M.} and Jarvik, {Gail P.} and Goddard, {Katrina A.B.} and Wilfond, {Benjamin S.}",

note = "Funding Information: National Human Genome Research Institute, Grant/Award Number: R01 CA154517, R01 HG006600, R01 HG006618, R01 HG008605, U01 HG006485, U01 HG006487, U01 HG006492, U01 HG006500, U01 HG006507, U01 HG006546, U01 HG007307, UM1 HG007301, UM1 HG007292; Intramural Research Program of the National Human Genome Research Institute, Grant/Award Number: ZIA HG20038703 Funding Information: The authors thank all of the clinical sequencing exploratory research (CSER) staff and participants for their support and involvement in this research. This work was supported by grants from the National Human Genome Research Institute and National Cancer Institute (U01 HG006485, MPI: Plon, Parsons; U01 HG006500, PI: Green; U01 HG006546, MPI: Krantz, Spinner; U01 HG006492, MPI: van Allen, Janne; UM1 HG007301, MPI: Myers, Cooper; UM1 HG007292, MPI: Goddard, Wilfond; U01 HG006487, MPI: Evans, Berg, Henderson; U01 HG006507, PI: Jarvik; R01 HG006600, PI: Chung; R01 HG006618, PI: Tabor; R01 CA154517, MPI: Petersen, Koenig, Wolf; R01 HG008605, MPI: Wolf, Clayton, Lawrenz; with additional support from U01 HG007307 (Coordinating Center)) as part of the clinical sequencing exploratory research (CSER) consortium. The ClinSeq project was supported by the Intramural Research Program of the National Human Genome Research Institute (ZIA HG20038703, PI: Biesecker). Publisher Copyright: {\textcopyright} 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.",

year = "2018",

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language = "English (US)",

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TY - JOUR

T1 - Approaches to carrier testing and results disclosure in translational genomics research

T2 - The clinical sequencing exploratory research consortium experience

AU - The members of the CSER Actionability and Return of Results Working Group

AU - Porter, Kathryn M.

AU - Kauffman, Tia L.

AU - Koenig, Barbara A.

AU - Lewis, Katie L.

AU - Rehm, Heidi L.

AU - Richards, Carolyn Sue

AU - Strande, Natasha T.

AU - Tabor, Holly K.

AU - Wolf, Susan M.

AU - Yang, Yaping

AU - Amendola, Laura M.

AU - Azzariti, Danielle R.

AU - Berg, Jonathan S.

AU - Bergstrom, Katie

AU - Biesecker, Leslie G.

AU - Biswas, Sawona

AU - Bowling, Kevin M.

AU - Chung, Wendy K.

AU - Clayton, Ellen W.

AU - Conlin, Laura K.

AU - Cooper, Gregory M.

AU - Dulik, Matthew C.

AU - Garraway, Levi A.

AU - Ghazani, Arezou A.

AU - Green, Robert C.

AU - Hiatt, Susan M.

AU - Jamal, Seema M.

AU - Jarvik, Gail P.

AU - Goddard, Katrina A.B.

AU - Wilfond, Benjamin S.

N1 - Funding Information: National Human Genome Research Institute, Grant/Award Number: R01 CA154517, R01 HG006600, R01 HG006618, R01 HG008605, U01 HG006485, U01 HG006487, U01 HG006492, U01 HG006500, U01 HG006507, U01 HG006546, U01 HG007307, UM1 HG007301, UM1 HG007292; Intramural Research Program of the National Human Genome Research Institute, Grant/Award Number: ZIA HG20038703 Funding Information: The authors thank all of the clinical sequencing exploratory research (CSER) staff and participants for their support and involvement in this research. This work was supported by grants from the National Human Genome Research Institute and National Cancer Institute (U01 HG006485, MPI: Plon, Parsons; U01 HG006500, PI: Green; U01 HG006546, MPI: Krantz, Spinner; U01 HG006492, MPI: van Allen, Janne; UM1 HG007301, MPI: Myers, Cooper; UM1 HG007292, MPI: Goddard, Wilfond; U01 HG006487, MPI: Evans, Berg, Henderson; U01 HG006507, PI: Jarvik; R01 HG006600, PI: Chung; R01 HG006618, PI: Tabor; R01 CA154517, MPI: Petersen, Koenig, Wolf; R01 HG008605, MPI: Wolf, Clayton, Lawrenz; with additional support from U01 HG007307 (Coordinating Center)) as part of the clinical sequencing exploratory research (CSER) consortium. The ClinSeq project was supported by the Intramural Research Program of the National Human Genome Research Institute (ZIA HG20038703, PI: Biesecker). Publisher Copyright: © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

PY - 2018/11

Y1 - 2018/11

N2 - Background: Clinical genome and exome sequencing (CGES) is primarily used to address specific clinical concerns by detecting risk of future disease, clarifying diagnosis, or directing treatment. Additionally, CGES makes possible the disclosure of autosomal recessive and X-linked carrier results as additional secondary findings, and research about the impact of carrier results disclosure in this context is needed. Methods: Representatives from 11 projects in the clinical sequencing exploratory research (CSER) consortium collected data from their projects using a structured survey. The survey focused on project characteristics, which variants were offered and/or disclosed to participants as carrier results, methods for carrier results disclosure, and project-specific outcomes. We recorded quantitative responses and report descriptive statistics with the aim of describing the variability in approaches to disclosing carrier results in translational genomics research projects. Results: The proportion of participants with carrier results was related to the number of genes included, ranging from 3% (three genes) to 92% (4,600 genes). Between one and seven results were disclosed to those participants who received any positive result. Most projects offered participants choices about whether to receive some or all of the carrier results. There were a range of approaches to communicate results, and many projects used separate approaches for disclosing positive and negative results. Conclusion: Future translational genomics research projects will need to make decisions regarding whether and how to disclose carrier results. The CSER consortium experience identifies approaches that balance potential participant interest while limiting impact on project resources.

AB - Background: Clinical genome and exome sequencing (CGES) is primarily used to address specific clinical concerns by detecting risk of future disease, clarifying diagnosis, or directing treatment. Additionally, CGES makes possible the disclosure of autosomal recessive and X-linked carrier results as additional secondary findings, and research about the impact of carrier results disclosure in this context is needed. Methods: Representatives from 11 projects in the clinical sequencing exploratory research (CSER) consortium collected data from their projects using a structured survey. The survey focused on project characteristics, which variants were offered and/or disclosed to participants as carrier results, methods for carrier results disclosure, and project-specific outcomes. We recorded quantitative responses and report descriptive statistics with the aim of describing the variability in approaches to disclosing carrier results in translational genomics research projects. Results: The proportion of participants with carrier results was related to the number of genes included, ranging from 3% (three genes) to 92% (4,600 genes). Between one and seven results were disclosed to those participants who received any positive result. Most projects offered participants choices about whether to receive some or all of the carrier results. There were a range of approaches to communicate results, and many projects used separate approaches for disclosing positive and negative results. Conclusion: Future translational genomics research projects will need to make decisions regarding whether and how to disclose carrier results. The CSER consortium experience identifies approaches that balance potential participant interest while limiting impact on project resources.

KW - carrier testing

KW - exome

KW - genome

KW - secondary findings

KW - translational genomics research

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U2 - 10.1002/mgg3.453

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SN - 2324-9269

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EP - 909

JO - Molecular Genetics and Genomic Medicine

JF - Molecular Genetics and Genomic Medicine

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Approaches to carrier testing and results disclosure in translational genomics research: The clinical sequencing exploratory research consortium experience

Abstract

Bibliographical note

Keywords

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