The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network

Kathleen A. Leppig; Alanna Kulchak Rahm; Paul Appelbaum; Sharon Aufox; Harris T. Bland; Adam Buchanan; Kurt D. Christensen; Wendy K. Chung; Ellen Wright Clayton; David Crosslin; Josh Denny; Shannon DeVange; Adam Gordon; Robert C. Green; Hakon Hakonarson; Margaret H. Harr; Nora Henrikson; Christin Hoell; Ingrid A. Holm; Iftikhar J. Kullo; Gail P. Jarvik; Philip E. Lammers; Eric B. Larson; Noralane M. Lindor; Maddalena Marasa; Melanie F. Myers; Emma Perez; Josh F. Peterson; Siddharth Pratap; Cynthia A. Prows; James D. Ralston; Hila Milo Rasouly; Dan M. Roden; Richard R. Sharp; Rajbir Singh; Gabriel Shaibi; Maureen E. Smith; Amy Sturm; Heidi A. Thiese; Sara L. Van Driest; Janet Williams; Marc S. Williams; Julia Wynn; Carrie L. Blout Zawatsky; Georgia L. Wiesner

doi:10.1016/j.gim.2022.01.015

The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network

Kathleen A. Leppig^*, Alanna Kulchak Rahm, Paul Appelbaum, Sharon Aufox, Harris T. Bland, Adam Buchanan, Kurt D. Christensen, Wendy K. Chung, Ellen Wright Clayton, David Crosslin, Josh Denny, Shannon DeVange, Adam Gordon, Robert C. Green, Hakon Hakonarson, Margaret H. Harr, Nora Henrikson, Christin Hoell, Ingrid A. Holm, Iftikhar J. KulloGail P. Jarvik, Philip E. Lammers, Eric B. Larson, Noralane M. Lindor, Maddalena Marasa, Melanie F. Myers, Emma Perez, Josh F. Peterson, Siddharth Pratap, Cynthia A. Prows, James D. Ralston, Hila Milo Rasouly, Dan M. Roden, Richard R. Sharp, Rajbir Singh, Gabriel Shaibi, Maureen E. Smith, Amy Sturm, Heidi A. Thiese, Sara L. Van Driest, Janet Williams, Marc S. Williams, Julia Wynn, Carrie L. Blout Zawatsky, Georgia L. Wiesner

^*Corresponding author for this work

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

17 Scopus citations

Abstract

Purpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants. Methods: RoR processes were developed and approved by each eMERGE institution's internal review board. Investigators at each eMERGE3 site were surveyed for RoR processes related to the participant's disclosure of pathogenic or likely pathogenic variants and engagement with genetic counseling. Standard statistical analysis was performed. Results: Of the 25,084 eMERGE participants, 1444 had a pathogenic or likely pathogenic variant identified on the eMERGEseq panel of 67 genes and 14 single nucleotide variants. Of these, 1077 (74.6%) participants had results disclosed, with 562 (38.9%) participants provided with variant-specific genetic counseling. Site-specific processes that either offered or required genetic counseling in their RoR process had an effect on whether a participant ultimately engaged with genetic counseling (P =.0052). Conclusion: The real-life experience of the multiarm eMERGE3 RoR study for returning actionable genomic results to consented research participants showed the impact of consent, method of disclosure, and genetic counseling on RoR.

Original language	English (US)
Pages (from-to)	1130-1138
Number of pages	9
Journal	Genetics in Medicine
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.gim.2022.01.015
State	Published - May 2022

Funding

The authors thank the Coordinating Center for the Electronic Medical Records and Genomics (eMERGE) Network for assistance in meeting and technical support. This phase of the eMERGE Network was initiated and funded by the National Human Genome Research Institute through the following grants: U01HG008657 (Group Health Cooperative/University of Washington), U01HG008685 (Brigham and Women's Hospital), U01HG008672 (Vanderbilt University Medical Center), U01HG008666 (Cincinnati Children's Hospital Medical Center), U01HG006379 (Mayo Clinic), U01HG008679 (Geisinger Clinic), U01HG008680 (Columbia University Health Sciences), U01HG008684 (Children's Hospital of Philadelphia), U01HG008673 (Northwestern University), U01HG008701 (Vanderbilt University Medical Center serving as the Coordinating Center), U01HG008676 (Partners Healthcare/Broad Institute), U54MD007593-10 (Meharry Medical College), and U01HG008664 (Baylor College of Medicine). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Conceptualization K.A.L. I.A.H. I.J.K. A.K.R. G.L.W.; Data Curation: S.A. A.B. S.D. M.H.H. C.H. N.M.L. M.M. M.F.M. E.P. C.A.P. H.M.R. R.S. G.S. M.E.S. A.S. H.A.T. J.W. C.L.B.Z.; Formal Analysis: K.A.L. A.K.R. G.L.W.; Funding Acquisition: E.B.L. I.J.K. D.M.R. M.S.W. G.P.J.; Investigation: K.A.L. P.A. K.D.C. W.K.C. E.W.C. D.C. J.D. A.G. R.C.G. H.H. N.H. P.E.L. J.F.P. S.P. J.D.R. R.R.S. S.L.V.D. G.L.W.; Methodology; K.A.L. A.K.R. G.L.W.; Project Administration: S.T.B. This study was reviewed and approved by the Institutional Review Board and Human Subjects Committee of each of the 10 institutions involved in the Electronic Medical Records and Genomics Phase III (eMERGE3) Network: Cincinnati Children's Hospital and Medical Center, Children's Hospital of Philadelphia, Columbia University, Geisinger, Kaiser Permanente of Washington/University of Washington, Mayo Clinic, Meharry Medical Center, Northwestern University, Partners Healthcare Center, and Vanderbilt University Medical Center. This phase of the eMERGE Network was initiated and funded by the National Human Genome Research Institute through the following grants: U01HG008657 ( Group Health Cooperative/University of Washington ), U01HG008685 ( Brigham and Women's Hospital ), U01HG008672 ( Vanderbilt University Medical Center ), U01HG008666 ( Cincinnati Children's Hospital Medical Center ), U01HG006379 ( Mayo Clinic ), U01HG008679 ( Geisinger Clinic ), U01HG008680 ( Columbia University Health Sciences ), U01HG008684 ( Children's Hospital of Philadelphia ), U01HG008673 ( Northwestern University ), U01HG008701 ( Vanderbilt University Medical Center serving as the Coordinating Center), U01HG008676 ( Partners Healthcare/Broad Institute ), U54MD007593-10 ( Meharry Medical College ), and U01HG008664 ( Baylor College of Medicine ). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Keywords

Consent
Genetic counseling
Genomic medicine
Return of results
eMERGE

ASJC Scopus subject areas

Genetics(clinical)

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10.1016/j.gim.2022.01.015

Cite this

Leppig, K. A., Kulchak Rahm, A., Appelbaum, P., Aufox, S., Bland, H. T., Buchanan, A., Christensen, K. D., Chung, W. K., Clayton, E. W., Crosslin, D., Denny, J., DeVange, S., Gordon, A., Green, R. C., Hakonarson, H., Harr, M. H., Henrikson, N., Hoell, C., Holm, I. A., ... Wiesner, G. L. (2022). The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network. Genetics in Medicine, 24(5), 1130-1138. https://doi.org/10.1016/j.gim.2022.01.015

@article{43060c8647e448219f048f76b186e01c,

title = "The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network",

abstract = "Purpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants. Methods: RoR processes were developed and approved by each eMERGE institution's internal review board. Investigators at each eMERGE3 site were surveyed for RoR processes related to the participant's disclosure of pathogenic or likely pathogenic variants and engagement with genetic counseling. Standard statistical analysis was performed. Results: Of the 25,084 eMERGE participants, 1444 had a pathogenic or likely pathogenic variant identified on the eMERGEseq panel of 67 genes and 14 single nucleotide variants. Of these, 1077 (74.6%) participants had results disclosed, with 562 (38.9%) participants provided with variant-specific genetic counseling. Site-specific processes that either offered or required genetic counseling in their RoR process had an effect on whether a participant ultimately engaged with genetic counseling (P =.0052). Conclusion: The real-life experience of the multiarm eMERGE3 RoR study for returning actionable genomic results to consented research participants showed the impact of consent, method of disclosure, and genetic counseling on RoR.",

keywords = "Consent, Genetic counseling, Genomic medicine, Return of results, eMERGE",

author = "Leppig, {Kathleen A.} and {Kulchak Rahm}, Alanna and Paul Appelbaum and Sharon Aufox and Bland, {Harris T.} and Adam Buchanan and Christensen, {Kurt D.} and Chung, {Wendy K.} and Clayton, {Ellen Wright} and David Crosslin and Josh Denny and Shannon DeVange and Adam Gordon and Green, {Robert C.} and Hakon Hakonarson and Harr, {Margaret H.} and Nora Henrikson and Christin Hoell and Holm, {Ingrid A.} and Kullo, {Iftikhar J.} and Jarvik, {Gail P.} and Lammers, {Philip E.} and Larson, {Eric B.} and Lindor, {Noralane M.} and Maddalena Marasa and Myers, {Melanie F.} and Emma Perez and Peterson, {Josh F.} and Siddharth Pratap and Prows, {Cynthia A.} and Ralston, {James D.} and Rasouly, {Hila Milo} and Roden, {Dan M.} and Sharp, {Richard R.} and Rajbir Singh and Gabriel Shaibi and Smith, {Maureen E.} and Amy Sturm and Thiese, {Heidi A.} and {Van Driest}, {Sara L.} and Janet Williams and Williams, {Marc S.} and Julia Wynn and {Blout Zawatsky}, {Carrie L.} and Wiesner, {Georgia L.}",

note = "Publisher Copyright: {\textcopyright} 2022 American College of Medical Genetics and Genomics",

year = "2022",

month = may,

doi = "10.1016/j.gim.2022.01.015",

language = "English (US)",

volume = "24",

pages = "1130--1138",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Elsevier B.V.",

number = "5",

}

Leppig, KA, Kulchak Rahm, A, Appelbaum, P, Aufox, S, Bland, HT, Buchanan, A, Christensen, KD, Chung, WK, Clayton, EW, Crosslin, D, Denny, J, DeVange, S, Gordon, A, Green, RC, Hakonarson, H, Harr, MH, Henrikson, N, Hoell, C, Holm, IA, Kullo, IJ, Jarvik, GP, Lammers, PE, Larson, EB, Lindor, NM, Marasa, M, Myers, MF, Perez, E, Peterson, JF, Pratap, S, Prows, CA, Ralston, JD, Rasouly, HM, Roden, DM, Sharp, RR, Singh, R, Shaibi, G, Smith, ME, Sturm, A, Thiese, HA, Van Driest, SL, Williams, J, Williams, MS, Wynn, J, Blout Zawatsky, CL & Wiesner, GL 2022, 'The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network', Genetics in Medicine, vol. 24, no. 5, pp. 1130-1138. https://doi.org/10.1016/j.gim.2022.01.015

TY - JOUR

T1 - The reckoning

T2 - The return of genomic results to 1444 participants across the eMERGE3 Network

AU - Leppig, Kathleen A.

AU - Kulchak Rahm, Alanna

AU - Appelbaum, Paul

AU - Aufox, Sharon

AU - Bland, Harris T.

AU - Buchanan, Adam

AU - Christensen, Kurt D.

AU - Chung, Wendy K.

AU - Clayton, Ellen Wright

AU - Crosslin, David

AU - Denny, Josh

AU - DeVange, Shannon

AU - Gordon, Adam

AU - Green, Robert C.

AU - Hakonarson, Hakon

AU - Harr, Margaret H.

AU - Henrikson, Nora

AU - Hoell, Christin

AU - Holm, Ingrid A.

AU - Kullo, Iftikhar J.

AU - Jarvik, Gail P.

AU - Lammers, Philip E.

AU - Larson, Eric B.

AU - Lindor, Noralane M.

AU - Marasa, Maddalena

AU - Myers, Melanie F.

AU - Perez, Emma

AU - Peterson, Josh F.

AU - Pratap, Siddharth

AU - Prows, Cynthia A.

AU - Ralston, James D.

AU - Rasouly, Hila Milo

AU - Roden, Dan M.

AU - Sharp, Richard R.

AU - Singh, Rajbir

AU - Shaibi, Gabriel

AU - Smith, Maureen E.

AU - Sturm, Amy

AU - Thiese, Heidi A.

AU - Van Driest, Sara L.

AU - Williams, Janet

AU - Williams, Marc S.

AU - Wynn, Julia

AU - Blout Zawatsky, Carrie L.

AU - Wiesner, Georgia L.

PY - 2022/5

Y1 - 2022/5

N2 - Purpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants. Methods: RoR processes were developed and approved by each eMERGE institution's internal review board. Investigators at each eMERGE3 site were surveyed for RoR processes related to the participant's disclosure of pathogenic or likely pathogenic variants and engagement with genetic counseling. Standard statistical analysis was performed. Results: Of the 25,084 eMERGE participants, 1444 had a pathogenic or likely pathogenic variant identified on the eMERGEseq panel of 67 genes and 14 single nucleotide variants. Of these, 1077 (74.6%) participants had results disclosed, with 562 (38.9%) participants provided with variant-specific genetic counseling. Site-specific processes that either offered or required genetic counseling in their RoR process had an effect on whether a participant ultimately engaged with genetic counseling (P =.0052). Conclusion: The real-life experience of the multiarm eMERGE3 RoR study for returning actionable genomic results to consented research participants showed the impact of consent, method of disclosure, and genetic counseling on RoR.

AB - Purpose: The goal of Electronic Medical Records and Genomics (eMERGE) Phase III Network was to return actionable sequence variants to 25,084 consenting participants from 10 different health care institutions across the United States. The purpose of this study was to evaluate system-based issues relating to the return of results (RoR) disclosure process for clinical grade research genomic tests to eMERGE3 participants. Methods: RoR processes were developed and approved by each eMERGE institution's internal review board. Investigators at each eMERGE3 site were surveyed for RoR processes related to the participant's disclosure of pathogenic or likely pathogenic variants and engagement with genetic counseling. Standard statistical analysis was performed. Results: Of the 25,084 eMERGE participants, 1444 had a pathogenic or likely pathogenic variant identified on the eMERGEseq panel of 67 genes and 14 single nucleotide variants. Of these, 1077 (74.6%) participants had results disclosed, with 562 (38.9%) participants provided with variant-specific genetic counseling. Site-specific processes that either offered or required genetic counseling in their RoR process had an effect on whether a participant ultimately engaged with genetic counseling (P =.0052). Conclusion: The real-life experience of the multiarm eMERGE3 RoR study for returning actionable genomic results to consented research participants showed the impact of consent, method of disclosure, and genetic counseling on RoR.

KW - Consent

KW - Genetic counseling

KW - Genomic medicine

KW - Return of results

KW - eMERGE

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UR - http://www.scopus.com/inward/citedby.url?scp=85125120295&partnerID=8YFLogxK

U2 - 10.1016/j.gim.2022.01.015

DO - 10.1016/j.gim.2022.01.015

M3 - Article

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AN - SCOPUS:85125120295

SN - 1098-3600

VL - 24

SP - 1130

EP - 1138

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 5

ER -

The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network

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