Return of individual results in epilepsy genomic research: A view from the field

Epilepsy Return of Results Workshop Participants

doi:10.1111/epi.14530

Return of individual results in epilepsy genomic research: A view from the field

Epilepsy Return of Results Workshop Participants

Pediatrics

Research output: Contribution to journal › Comment/debate › peer-review

8 Scopus citations

Abstract

Genomic findings are emerging rapidly in 2 large, closely related epilepsy research consortia: the Epilepsy Phenome/Genome Project and Epi4K. Disclosure of individual results to participants in genomic research is increasingly viewed as an ethical obligation, but strategies for return of results were not included in the design of these consortia, raising complexities in establishing criteria for which results to offer, determining participant preferences, managing the large number of sites involved, and covering associated costs. Here, we describe the challenges faced, alternative approaches considered, and progress to date. Experience from these 2 consortia illustrates the importance, for genomic research in epilepsy and other disorders, of including a specific plan for return of results in the study design, with financial support for obtaining clinical confirmation and providing ongoing support for participants. Participant preferences for return of results should be established at the time of enrollment, and methods for allowing future contacts with participants should be included. In addition, methods should be developed for summarizing meaningful, comprehensible information about findings in the aggregate that participants can access in an ongoing way.

Original language	English (US)
Pages (from-to)	1635-1642
Number of pages	8
Journal	Epilepsia
Volume	59
Issue number	9
DOIs	https://doi.org/10.1111/epi.14530
State	Published - Sep 2018

Funding

Ongoing contact with participants would be beneficial because it would enable the research team to offer them support for understanding and managing the findings. Furthermore, the sequencing results may be reinterpreted over time as new epilepsy‐related findings emerge, and we would like to be able to offer these reinterpreted results to the participants. The epilepsy community is well positioned for variant reinterpretation through the Epilepsy Genetics Initiative (EGI; www.cureepilepsy.org/egi/), a research effort jointly sponsored by Citizens United for Research in Epilepsy (CURE) and the National Institute of Neurologic Disorders and Stroke. In EGI, patients undergoing clinical sequencing are invited to deposit their sequence data, along with some clinical information, in a repository where data are reanalyzed every 6 months, allowing for discovery of novel genes or pathogenic variants in genes that have recently been published as causative for epilepsy. In the case of clinical sequencing, new findings from the EGI reanalysis are reported back to the physician who ordered the test. However, for participants in Epi4K, return of results from reanalysis presents the same complexities as return of the initial findings. The Return of Results in Epilepsy Genomic Research Workshop was funded by the Ron and Sanne Higgins Epilepsy Research Fund; this funder had no role in the writing of the manuscript. Authors of this manuscript were supported by grants from the US National Institute of Neurological Disorders and Stroke (U01NS077303 [HCM], U01NS077274 [DHL], U01NS077276 [DHL, RO], U01NS077367 [RO], R01NS078419 [RO], R01NS073872 [RO], K23NS069784 [AP], R01NS069605 [HCM]), and the US National Human Genome Research Institute (P50HG007257 [RO]).

Keywords

epileptic encephalopathy
genetics
pathogenic variants
research ethics

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1111/epi.14530

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title = "Return of individual results in epilepsy genomic research: A view from the field",

abstract = "Genomic findings are emerging rapidly in 2 large, closely related epilepsy research consortia: the Epilepsy Phenome/Genome Project and Epi4K. Disclosure of individual results to participants in genomic research is increasingly viewed as an ethical obligation, but strategies for return of results were not included in the design of these consortia, raising complexities in establishing criteria for which results to offer, determining participant preferences, managing the large number of sites involved, and covering associated costs. Here, we describe the challenges faced, alternative approaches considered, and progress to date. Experience from these 2 consortia illustrates the importance, for genomic research in epilepsy and other disorders, of including a specific plan for return of results in the study design, with financial support for obtaining clinical confirmation and providing ongoing support for participants. Participant preferences for return of results should be established at the time of enrollment, and methods for allowing future contacts with participants should be included. In addition, methods should be developed for summarizing meaningful, comprehensible information about findings in the aggregate that participants can access in an ongoing way.",

keywords = "epileptic encephalopathy, genetics, pathogenic variants, research ethics",

author = "{Epilepsy Return of Results Workshop Participants} and Ruth Ottman and Catharine Freyer and Mefford, {Heather C.} and Annapurna Poduri and Lowenstein, {Daniel H.} and Appelbaum, {Paul S.} and Wylie Burke and Tracy Dixon-Salazar and Dennis Dlugos and Fisher, {Robert S.} and Helbig, {Katherine L.} and Laurie Herraiz and Ingrid Holm and Melanie Huntley and Barbara Koenig and Laux, {Linda C.} and Brenda Porter and Shannon Sewards and Sheidley, {Beth R.}",

note = "Publisher Copyright: Wiley Periodicals, Inc. {\textcopyright} 2018 International League Against Epilepsy",

year = "2018",

month = sep,

doi = "10.1111/epi.14530",

language = "English (US)",

volume = "59",

pages = "1635--1642",

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AU - Burke, Wylie

AU - Dixon-Salazar, Tracy

AU - Dlugos, Dennis

AU - Fisher, Robert S.

AU - Helbig, Katherine L.

AU - Herraiz, Laurie

AU - Holm, Ingrid

AU - Huntley, Melanie

AU - Koenig, Barbara

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AU - Porter, Brenda

AU - Sewards, Shannon

AU - Sheidley, Beth R.

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Return of individual results in epilepsy genomic research: A view from the field

Abstract

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Keywords

ASJC Scopus subject areas

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