Return of Results in Genomic Research Using Large-Scale or Whole Genome Sequencing: Toward a New Normal

Overview

Journal Annu Rev Genomics Hum Genet

Publisher Annual Reviews

Specialty Genetics

Date 2023 Mar 13

PMID 36913714

Authors

Susan M Wolf

Robert C Green

Affiliations

Soon will be listed here.

Abstract

Genome sequencing is increasingly used in research and integrated into clinical care. In the research domain, large-scale analyses, including whole genome sequencing with variant interpretation and curation, virtually guarantee identification of variants that are pathogenic or likely pathogenic and actionable. Multiple guidelines recommend that findings associated with actionable conditions be offered to research participants in order to demonstrate respect for autonomy, reciprocity, and participant interests in health and privacy. Some recommendations go further and support offering a wider range of findings, including those that are not immediately actionable. In addition, entities covered by the US Health Insurance Portability and Accountability Act (HIPAA) may be required to provide a participant's raw genomic data on request. Despite these widely endorsed guidelines and requirements, the implementation of return of genomic results and data by researchers remains uneven. This article analyzes the ethical and legal foundations for researcher duties to offer adult participants their interpreted results and raw data as the new normal in genomic research.

Citing Articles

Returning raw genomic data to research participants in a pediatric cancer precision medicine trial.

Barlow-Stewart K, Courtney E, Cowley M, Ebzery C, Fuentes Bolanos N, Gifford A NPJ Genom Med. 2025; 10(1):12.

PMID: 39962063 PMC: 11832931. DOI: 10.1038/s41525-025-00470-y.

Expert Stakeholder Perspectives on Emerging Technology for Neuroimaging Research with Highly Portable MRI: The Need for Guidance on Ethical, Legal, and Societal Issues.

Madzelan M, Lawrenz F, Wolf S, Shen F J Law Med Ethics. 2025; 52(4):786-804.

PMID: 39885743 PMC: 11798672. DOI: 10.1017/jme.2024.160.

Returning genetic risk information for hereditary cancers to participants in a population-based cohort study in Japan.

Ohneda K, Suzuki Y, Hamanaka Y, Tadaka S, Shimada M, Hasegawa-Minato J J Hum Genet. 2025; 70(3):147-157.

PMID: 39825003 PMC: 11802448. DOI: 10.1038/s10038-024-01314-w.

Patient safety and healthcare quality of U.S. laboratory developed tests (LDTs) in the AI/ML era of precision medicine.

Kurnat-Thoma E Front Mol Biosci. 2024; 11:1407513.

PMID: 39165642 PMC: 11334219. DOI: 10.3389/fmolb.2024.1407513.

All of Us participant perspectives on the return of value in research.

Richmond J, Cunningham-Erves J, Givens B, Guide A, Barnes L, Fair A Genet Med. 2024; 26(8):101163.

PMID: 38738530 PMC: 11298296. DOI: 10.1016/j.gim.2024.101163.

References

Blout Zawatsky C, Shah N, Machini K, Perez E, Christensen K, Zouk H . Returning actionable genomic results in a research biobank: Analytic validity, clinical implementation, and resource utilization. Am J Hum Genet. 2021; 108(12):2224-2237. PMC: 8715145. DOI: 10.1016/j.ajhg.2021.10.005. View

Scherr C, Aufox S, Ross A, Ramesh S, Wicklund C, Smith M . What People Want to Know About Their Genes: A Critical Review of the Literature on Large-Scale Genome Sequencing Studies. Healthcare (Basel). 2018; 6(3). PMC: 6165341. DOI: 10.3390/healthcare6030096. View

Thorogood A, Bobe J, Prainsack B, Middleton A, Scott E, Nelson S . APPLaUD: access for patients and participants to individual level uninterpreted genomic data. Hum Genomics. 2018; 12(1):7. PMC: 5816450. DOI: 10.1186/s40246-018-0139-5. View

Koplin J, Savulescu J, Vears D . Why genomics researchers are sometimes morally required to hunt for secondary findings. BMC Med Ethics. 2020; 21(1):11. PMC: 6995186. DOI: 10.1186/s12910-020-0449-8. View

Kohane I, Mandl K, Taylor P, Holm I, Nigrin D, Kunkel L . Medicine. Reestablishing the researcher-patient compact. Science. 2007; 316(5826):836-7. DOI: 10.1126/science.1135489. View

Gordon D, Breitkopf C, Robinson M, Petersen W, Egginton J, Chaffee K . Should Researchers Offer Results to Family Members of Cancer Biobank Participants? A Mixed-Methods Study of Proband and Family Preferences. AJOB Empir Bioeth. 2019; 10(1):1-22. PMC: 6443426. DOI: 10.1080/23294515.2018.1546241. View

Reble E, Salazar M, Zakoor K, Khalouei S, Clausen M, Kodida R . Beyond medically actionable results: an analytical pipeline for decreasing the burden of returning all clinically significant secondary findings. Hum Genet. 2020; 140(3):493-504. DOI: 10.1007/s00439-020-02220-9. View

Sayeed S, Califf R, Green R, Wong C, Mahaffey K, Gambhir S . Return of individual research results: What do participants prefer and expect?. PLoS One. 2021; 16(7):e0254153. PMC: 8320928. DOI: 10.1371/journal.pone.0254153. View

Illes J, Kirschen M, Edwards E, Stanford L, Bandettini P, Cho M . Ethics. Incidental findings in brain imaging research. Science. 2006; 311(5762):783-4. PMC: 1524853. DOI: 10.1126/science.1124665. View

10.

Green R, Berg J, Grody W, Kalia S, Korf B, Martin C . ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013; 15(7):565-74. PMC: 3727274. DOI: 10.1038/gim.2013.73. View

11.

Wolf S, Evans B . Return of results and data to study participants. Science. 2018; 362(6411):159-160. DOI: 10.1126/science.aav0005. View

12.

Hallowell N, Hall A, Alberg C, Zimmern R . Revealing the results of whole-genome sequencing and whole-exome sequencing in research and clinical investigations: some ethical issues. J Med Ethics. 2014; 41(4):317-21. DOI: 10.1136/medethics-2013-101996. View

13.

Wolf S, Crock B, Van Ness B, Lawrenz F, Kahn J, Beskow L . Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med. 2012; 14(4):361-84. PMC: 3597341. DOI: 10.1038/gim.2012.23. View

14.

. ASHG statement. Professional disclosure of familial genetic information. The American Society of Human Genetics Social Issues Subcommittee on Familial Disclosure. Am J Hum Genet. 1998; 62(2):474-83. PMC: 1376910. View

15.

David K, Best R, Brenman L, Bush L, Deignan J, Flannery D . Patient re-contact after revision of genomic test results: points to consider-a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018; 21(4):769-771. DOI: 10.1038/s41436-018-0391-z. View

16.

Knoppers B, Deschenes M, Zawati M, Tasse A . Population studies: return of research results and incidental findings Policy Statement. Eur J Hum Genet. 2012; 21(3):245-7. PMC: 3573193. DOI: 10.1038/ejhg.2012.152. View

17.

Joffe S, Sellers D, Ekunwe L, Antoine-LaVigne D, McGraw S, Levy D . Preferences for Return of Genetic Results Among Participants in the Jackson Heart Study and Framingham Heart Study. Circ Genom Precis Med. 2019; 12(12):e002632. PMC: 7173999. DOI: 10.1161/CIRCGEN.119.002632. View

18.

Carrieri D, Howard H, Benjamin C, Clarke A, Dheensa S, Doheny S . Recontacting patients in clinical genetics services: recommendations of the European Society of Human Genetics. Eur J Hum Genet. 2018; 27(2):169-182. PMC: 6336881. DOI: 10.1038/s41431-018-0285-1. View

19.

Wolf S, Paradise J, Caga-Anan C . The law of incidental findings in human subjects research: establishing researchers' duties. J Law Med Ethics. 2008; 36(2):361-83, 214. PMC: 2581517. DOI: 10.1111/j.1748-720X.2008.00281.x. View

20.

Wolf S, Evans B . Defending the return of results and data. Science. 2018; 362(6420):1255-1256. DOI: 10.1126/science.aaw1851. View