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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.

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2023-08-25
2024-06-22
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Literature Cited

  1. 1.
    Abul-Husn NS, Soper ER, Braganza GT, Rodriguez JE, Zeid N et al. 2021. Implementing genomic screening in diverse populations. Genome Med. 13:17
    [Google Scholar]
  2. 2.
    ACMG Board Dir 2012. Points to consider in the clinical application of genomic sequencing. Genet. Med. 14:759–61
    [Google Scholar]
  3. 3.
    ACMG Board Dir 2015. ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. Genet. Med. 17:68–69
    [Google Scholar]
  4. 4.
    ACMG Board Dir 2015. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet. Med. 17:505–7
    [Google Scholar]
  5. 5.
    Allen NL, Karlson EW, Malspeis S, Lu B, Seidman CE, Lehmann LS. 2014. Biobank participants’ preferences for disclosure of genetic research results: perspectives from the OurGenes, OurHealth, OurCommunity project. Mayo Clin. Proc. 89:738–46
    [Google Scholar]
  6. 6.
    Am. Soc. Hum. Genet. Soc. Issues Subcomm. Fam. Discl 1998. Professional disclosure of familial genetic information. Am. J. Hum. Genet. 62:474–83
    [Google Scholar]
  7. 7.
    Amendola LM, Robinson JO, Hart R, Biswas S, Lee K et al. 2018. Why patients decline genomic sequencing studies: experiences from the CSER Consortium. J. Genet. Couns. 27:1220–27
    [Google Scholar]
  8. 8.
    Bacon PL, Harris ED, Ziniel SI, Savage SK, Weitzman ER et al. 2015. The development of a preference-setting model for the return of individual genomic research results. J. Empir. Res. Hum. Res. Ethics 10:107–20
    [Google Scholar]
  9. 9.
    Berkman BE. 2017. Refuting the right not to know. J. Health Care Law Policy 19:1–72
    [Google Scholar]
  10. 10.
    Beskow LM, Burke W. 2010. Offering individual genetic research results: context matters. Sci. Transl. Med. 2:38cm20
    [Google Scholar]
  11. 11.
    Beskow LM, Burke W, Merz JF, Barr PA, Terry S et al. 2001. Informed consent for population-based research involving genetics. JAMA 286:2315–21
    [Google Scholar]
  12. 12.
    Bledsoe MJ, Clayton EW, McGuire AL, Grizzle WE, O'Rourke PP et al. 2013. Return of results from genomic biobanks: cost matters. Genet. Med. 15:103–5
    [Google Scholar]
  13. 13.
    Bollinger JM, Scott J, Dvoskin R, Kaufman D. 2012. Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. Genet. Med. 14:451–57
    [Google Scholar]
  14. 14.
    Bombard Y, Brothers KB, Fitzgerald-Butt S, Garrison NA, Jamal L et al. 2019. The responsibility to recontact research participants after reinterpretation of genetic and genomic research results. Am. J. Hum. Genet. 104:578–95
    [Google Scholar]
  15. 15.
    Bookman EB, Langehorne AA, Eckfeldt JH, Glass KC, Jarvik GP et al. 2006. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. Am. J. Hum. Genet. A 140A:1033–40
    [Google Scholar]
  16. 16.
    Borgelt E, Anderson JA, Illes J. 2013. Managing incidental findings: lessons from neuroimaging. Am. J. Bioeth. 13:246–47
    [Google Scholar]
  17. 17.
    Boronow KE, Susmann HP, Gajos KZ, Rudel RA, Arnold KC et al. 2017. DERBI: a digital method to help researchers offer “right-to-know” personal exposure results. Environ. Health Perspect. 125:A27–33
    [Google Scholar]
  18. 18.
    Breitkopf CR, Petersen GM, Wolf SM, Chaffee KG, Robinson ME et al. 2015. Preferences regarding return of genomic results to relatives of research participants, including after participant death: empirical results from a cancer biobank. J. Law Med. Ethics 43:464–75
    [Google Scholar]
  19. 19.
    Bui ET, Anderson NK, Kassern L, McMahon FJ. 2014. Do participants in genome sequencing studies of psychiatric disorders wish to be informed of their results? A survey study. PLOS ONE 9:e101111
    [Google Scholar]
  20. 20.
    Burnett-Hartman AN, Blum-Barnett E, Carroll NM, Madrid SD, Jonas C et al. 2020. Return of research-related genetic test results and genetic discrimination concerns: facilitators and barriers of genetic research participation in diverse groups. Public Health Genom. 23:59–68
    [Google Scholar]
  21. 21.
    Carrieri D, Howard HC, Benjamin C, Clarke AJ, Dheensa S et al. 2019. Recontacting patients in clinical genetics services: recommendations of the European Society of Human Genetics. Eur. J. Hum. Genet. 27:169–82
    [Google Scholar]
  22. 22.
    Caulfield T, McGuire AL, Cho M, Buchanan JA, Burgess MM et al. 2008. Research ethics recommendations for whole-genome research: consensus statement. PLOS Biol. 6:e73
    [Google Scholar]
  23. 23.
    Christensen KD, Roberts JS, Uhlmann WR, Green RC. 2011. Changes to perceptions of the pros and cons of genetic susceptibility testing after APOE genotyping for Alzheimer disease risk. Genet. Med. 13:409–14
    [Google Scholar]
  24. 24.
    Christensen KD, Schonman EF, Robinson JO, Roberts JS, Diamond PM et al. 2021. Behavioral and psychological impact of genome sequencing: a pilot randomized trial of primary care and cardiology patients. Genom. Med. 6:72
    [Google Scholar]
  25. 25.
    Clayton EW, Evans BJ, Hazel JW, Rothstein MA. 2019. The law of genetic privacy: applications, implications, and limitations. J. Law Biosci. 6:1–36
    [Google Scholar]
  26. 26.
    Comber DA, Davies B, Roberts JD, Tadros R, Green MS et al. 2022. Return of results policies for genomic research: current practices and the Hearts in Rhythm Organization (HiRO) approach. Can. J. Cardiol. 38:526–35
    [Google Scholar]
  27. 27.
    Crawford DC, Cooke Bailey JN, Briggs FBS 2019. Mind the gap: resources required to receive, process and interpret research-returned whole genome data. Hum. Genet. 138:691–701
    [Google Scholar]
  28. 28.
    Darnell AJ, Austin H, Bluemke DA, Cannon RO III, Fischbeck K et al. 2016. A clinical service to support the return of secondary genomic findings in human research. Am. J. Hum. Genet. 98:435–41
    [Google Scholar]
  29. 29.
    David KL, Best RG, Manace Brenman L, Bush L, Deignan JL et al. 2019. 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. 21:769–71
    [Google Scholar]
  30. 30.
    de Boer IH, Alpers CE, Azeloglu EU, Balis UGJ, Barasch JM et al. 2021. Rationale and design of the Kidney Precision Medicine Project. Kidney Int. 99:498–510
    [Google Scholar]
  31. 31.
    Deignan JL, Chung WK, Kearney HM, Monaghan KG, Rehder CW et al. 2019. Points to consider in the reevaluation and reanalysis of genomic test results: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 21:1267–70
    [Google Scholar]
  32. 32.
    Delanne J, Nambot S, Chassagne A, Putois O, Pelissier A et al. 2019. Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives: a review of the literature. Eur. J. Med. Genet. 62:103529
    [Google Scholar]
  33. 33.
    Denny JC, Rutter JL, Goldstein DB, Philippakis A, Smoller JW et al. 2019. The “All of Us” Research Program. N. Engl. J. Med. 381:668–76
    [Google Scholar]
  34. 34.
    Dorschner MO, Amendola LM, Turner EH, Robertson PD, Shirts BH et al. 2013. Actionable, pathogenic incidental findings in 1,000 participants’ exomes. Am. J. Hum. Genet. 93:631–40
    [Google Scholar]
  35. 35.
    Evans BJ, Wolf SM. 2019. A Faustian bargain that undermines research participants’ privacy rights and return of results. Fla. Law Rev. 71:1281–345
    [Google Scholar]
  36. 36.
    Fabsitz RR, McGuire A, Sharp RR, Puggal M, Beskow LM et al. 2010. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circ. Cardiovasc. Genet. 3:574–80
    [Google Scholar]
  37. 37.
    Fullerton SM, Wolf WA, Brothers KB, Clayton EW, Crawford DC et al. 2012. Return of individual research results from genome-wide association studies: experience of the Electronic Medical Records and Genomics (eMERGE) Network. Genet. Med. 14:424–31
    [Google Scholar]
  38. 38.
    Genomes2People Res. Program 2021. The PopSeq Project. Genomes2People Research Program https://www.genomes2people.org/research/the-popseq-project
    [Google Scholar]
  39. 39.
    Glob. Alliance Genom. Health 2021. Policy on clinically actionable genomic research results Policy Doc., Glob. Alliance Genom. Health Toronto, Can: https://www.ga4gh.org/wp-content/uploads/2021-Policy-on-Clinically-Actionable-Genomic-Research-Results.pdf
    [Google Scholar]
  40. 40.
    Goddard KAB, Lee K, Buchanan AH, Powell BC, Hunter JE. 2022. Establishing the medical actionability of genomic variants. Annu. Rev. Genom. Hum. Genet. 23:173–92
    [Google Scholar]
  41. 41.
    Gordon AS, Zouk H, Venner E, Eng CM, Funke BH et al. 2020. Frequency of genomic secondary findings among 21,915 eMERGE network participants. Genet. Med. 22:1470–77
    [Google Scholar]
  42. 42.
    Gordon DR, Breitkopf CR, Robinson ME, Petersen WO, Egginton JS et al. 2019. Should researchers offer results to family members of cancer biobank participants? A mixed-methods study of proband and family preferences. AJOB Empir. Bioeth. 10:11–22
    [Google Scholar]
  43. 43.
    Green RC, Berg JS, Grody WW, Kalia SS, Korf BR et al. 2013. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet. Med. 15:565–74
    [Google Scholar]
  44. 44.
    Green RC, Goddard KAB, Jarvik GP, Amendola LM, Appelbaum PS et al. 2016. Clinical Sequencing Exploratory Research Consortium: accelerating evidence-based practice of genomic medicine. Am. J. Hum. Genet. 98:1051–66
    [Google Scholar]
  45. 45.
    Green RC, Lautenbach D, McGuire AL. 2015. GINA, genetic discrimination, and genomic medicine. N. Engl. J. Med. 372:397–99
    [Google Scholar]
  46. 46.
    Green RC, Roberts JS, Cupples LA, Relkin NR, Whitehouse PJ et al. 2009. Disclosure of APOE genotype for risk of Alzheimer's disease. N. Engl. J. Med. 361:245–54
    [Google Scholar]
  47. 47.
    Grimes v. Kennedy Krieger Institute, Inc., 782 A.2d 807 (Ct. App. Md 2001.)
  48. 48.
    Hallowell N, Hall A, Alberg C, Zimmern R. 2015. Revealing the results of whole-genome sequencing and whole-exome sequencing in research and clinical investigations: some ethical issues. J. Med. Ethics 41:317–21
    [Google Scholar]
  49. 49.
    Hart MR, Biesecker BB, Blout CL, Christensen KD, Amendola LM et al. 2019. Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study. Genet. Med. 21:1100–10
    [Google Scholar]
  50. 50.
    Hoell C, Wynn J, Rasmussen LV, Marsolo K, Aufox SA et al. 2020. Participant choices for return of genomic results in the eMERGE network. Genet. Med. 22:1821–29
    [Google Scholar]
  51. 51.
    Houdayer F, Putois O, Babonneau ML, Chaumet H, Joly L et al. 2019. Secondary findings from next generation sequencing: psychological and ethical issues: family and patient perspectives. Eur. J. Med. Genet. 62:103711
    [Google Scholar]
  52. 52.
    Illes J, Kirschen MP, Edwards E, Stanford LR, Bandettini P et al. 2006. Incidental findings in brain imaging research. Science 311:783–84
    [Google Scholar]
  53. 53.
    Jarvik GP, Amendola LM, Berg JS, Brothers K, Clayton EW et al. 2014. Return of results to research participants: the floor, the ceiling, and the choices in between. Am. J. Hum. Genet. 94:818–26
    [Google Scholar]
  54. 54.
    Jelsig AM, Qvist N, Brusgaard K, Bomme Ousager L. 2015. Research participants in NGS studies want to know about incidental findings. Eur. J. Hum. Genet. 23:1423–26
    [Google Scholar]
  55. 55.
    Joffe S, Sellers DE, Ekunwe L, Antoine-Lavigne D, McGraw S et al. 2019. Preferences for return of genetic results among participants in the Jackson Heart Study and Framingham Heart Study. Circ. Genom. Precis. Med. 12:552–60
    [Google Scholar]
  56. 56.
    Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C et al. 2017. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genom. Genet. Med. 19:249–55
    [Google Scholar]
  57. 57.
    Knoppers BM, Deschênes M, Zawati MH, Tassé AM. 2013. Population studies: return of research results and incidental findings policy statement. Eur. J. Hum. Genet. 21:245–47
    [Google Scholar]
  58. 58.
    Knoppers BM, Zawati MH, Sénécal K. 2015. Return of genetic testing results in the era of whole-genome sequencing. Nat. Rev. Genet. 16:553–59
    [Google Scholar]
  59. 59.
    Kohane IS, Mandl KD, Taylor PL, Holm IA, Nigrin DJ et al. 2007. Reestablishing the researcher-patient compact. Science 316:836–37
    [Google Scholar]
  60. 60.
    Kolata G. 2012. Genes now tell doctors secrets they can't utter. New York Times Aug. 25. https://www.nytimes.com/2012/08/26/health/research/with-rise-of-gene-sequencing-ethical-puzzles.html
    [Google Scholar]
  61. 61.
    Koplin JJ, Savulescu J, Vears DF. 2020. Why genomics researchers are sometimes morally required to hunt for secondary findings. BMC Med. Ethics 21:11
    [Google Scholar]
  62. 62.
    Lewis ACF, Knoppers BM, Green RC. 2021. An international policy on returning genomic research results. Genom. Med. 13:115
    [Google Scholar]
  63. 63.
    Lewis KL, Heidlebaugh AR, Epps S, Han PK, Fishler KP et al. 2019. Knowledge, motivations, expectations, and traits of an African, African-American, and Afro-Caribbean sequencing cohort and comparisons to the original ClinSeq® cohort. Genet. Med. 21:1355–62
    [Google Scholar]
  64. 64.
    Lockhart NC, Yassin R, Weil CJ, Compton CC. 2012. Intersection of biobanking and clinical care: Should discrepant diagnoses and pathological findings be returned to research participants?. Genet. Med. 14:417–23
    [Google Scholar]
  65. 65.
    Lunshof JE, Church GM, Prainsack B. 2014. Raw personal data: providing access. Science 343:373–74
    [Google Scholar]
  66. 66.
    Mackley MP, Fletcher B, Parker M, Watkins H, Ormondroyd E. 2017. Stakeholder views on secondary findings in whole-genome and whole-exome sequencing: a systematic review of quantitative and qualitative studies. Genet. Med. 19:283–93
    [Google Scholar]
  67. 67.
    Makhlouf MD. 2020. The ethics of DNA testing at the border. Am. J. Law Med. 46:253–73
    [Google Scholar]
  68. 68.
    Manrai AK, Funke BH, Rehm HL, Olesen MS, Maron BA et al. 2016. Genetic misdiagnoses and the potential for health disparities. N. Engl. J. Med. 375:655–65
    [Google Scholar]
  69. 69.
    McGuire AL, Caulfield T, Cho MK. 2008. Research ethics and the challenge of whole-genome sequencing. Nat. Rev. Genet. 9:152–56
    [Google Scholar]
  70. 70.
    Middleton A, Wright CF, Morley KI, Bragin E, Firth HV et al. 2015. Potential research participants support the return of raw sequence data. J. Med. Genet. 52:571–74
    [Google Scholar]
  71. 71.
    Miller DT, Lee K, Abul-Husn NS, Amendola LM, Brothers K et al. 2022. ACMG SF v3.1 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 24:1407–14
    [Google Scholar]
  72. 72.
    Miller DT, Lee K, Chung WK, Gordon AS, Herman GE et al. 2021. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 23:1381–90
    [Google Scholar]
  73. 73.
    Miller DT, Lee K, Gordon AS, Amendola LM, Adelman K et al. 2021. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 23:1391–98
    [Google Scholar]
  74. 74.
    Natl. Acad. Sci. Eng. Med 2018. Returning Individual Research Results to Participants: Guidance for a New Research Paradigm Washington, DC: Natl. Acad. Press
    [Google Scholar]
  75. 75.
    Natl. Bioeth. Advis. Comm 1999. Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, Vol. 1 Report and Recommendations of the National Bioethics Advisory Commission Rockville, MD: Natl. Bioeth. Advis. Comm.
    [Google Scholar]
  76. 76.
    Natl. Heart Lung Blood Inst. (NHLBI) Trans-Omics Precis. Med. (TOPMed) Program Ethical Leg. Soc. Issues (ELSI) Comm 2016. NHLBI TOPMed Program Ethical, Legal, and Social Issues (ELSI) Committee (DRAFT) report Rep. NHLBI Bethesda, MD: https://topmed.nhlbi.nih.gov/sites/default/files/TOPMed.ELSI.recommendations_1.v6.pdf
    [Google Scholar]
  77. 77.
    Natl. Inst. Health (NIH) All of Us Res. Program 2020. NIH's All of Us Research Program returns first genetic results to participants Program Announc. Dec. 10, NIH Bethesda, MD: https://allofus.nih.gov/news-events-and-media/announcements/nihs-all-us-research-program-returns-first-genetic-results-participants
    [Google Scholar]
  78. 78.
    O'Daniel JM, Ackerman S, Desrosiers LR, Rego S, Knight SJ et al.(CSER Stakehold. Engag. Work Group) 2022. Integration of stakeholder engagement from development to dissemination in genomic medicine research: approaches and outcomes from the CSER consortium. Genet. Med. 24:1108–19
    [Google Scholar]
  79. 79.
    O'Daniel JM, McLaughlin HM, Amendola LM, Bale SJ, Berg JS et al. 2017. A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories. Genet. Med. 19:575–82
    [Google Scholar]
  80. 80.
    Parens E, Appelbaum P, Chung W 2013. Incidental findings in the era of whole genome sequencing. Hastings Cent. Rep. 43:416–19
    [Google Scholar]
  81. 81.
    Popejoy AB, Fullerton SM. 2016. Genomics is failing on diversity. Nature 538:161–64
    [Google Scholar]
  82. 82.
    Precis. Med. Init. Work. Group 2015. The Precision Medicine Initiative Cohort Program – building a research foundation for 21st century medicine Rep. Precis: Med. Init. Work. Group https://acd.od.nih.gov/documents/reports/PMI_WG_report_2015-09-17-Final.pdf
    [Google Scholar]
  83. 83.
    Pres. Comm. Study Bioeth. Issues 2013. Anticipate and communicate: ethical management of incidental and secondary findings in the clinical, research, and direct-to-consumer contexts Rep. Pres. Comm. Study Bioeth. Issues Washington, DC: https://bioethicsarchive.georgetown.edu/pcsbi/sites/default/files/FINALAnticipateCommunicate_PCSBI_0.pdf
    [Google Scholar]
  84. 84.
    Ralefala D, Kasule M, Wonkam A, Matshaba M, de Vries J. 2020. Do solidarity and reciprocity obligations compel African researchers to feedback individual genetic results in genomics research?. BMC Med. Ethics 21:112
    [Google Scholar]
  85. 85.
    Ram N, Murphy EE, Suter SM. 2021. Regulating forensic genetic genealogy. Science 373:1444–46
    [Google Scholar]
  86. 86.
    Reble E, Salazar MG, Zakoor K-R, Khalouey S, Clausen M et al. 2021. Beyond medically actionable results: an analytic pipeline for decreasing the burden of returning all clinically significant secondary findings. Hum. Genet. 140:493–504
    [Google Scholar]
  87. 87.
    Reilly P. 1980. When should an investigator share raw data with the subjects?. IRB 2:94–5, 12
    [Google Scholar]
  88. 88.
    Richardson HS. 2008. Incidental findings and ancillary-care obligations. J. Law Med. Ethics 36:256–70
    [Google Scholar]
  89. 89.
    Richardson HS. 2012. Moral Entanglements: The Ancillary Care Obligations of Medical Researchers New York: Oxford Univ. Press
    [Google Scholar]
  90. 90.
    Richardson HS, Belsky L. 2004. The ancillary-care responsibilities of medical researchers: an ethical framework for thinking about the clinical care that researchers owe their subjects. Hastings Cent. Rep. 34:25–33
    [Google Scholar]
  91. 91.
    Roberts JS, Chen CA, Uhlmann WR, Green RC. 2012. Effectiveness of a condensed protocol for disclosing APOE genotype and providing risk education for Alzheimer disease. Genet. Med. 14:742–48
    [Google Scholar]
  92. 92.
    Roberts JS, Christensen KD, Green RC. 2011. Using Alzheimer's disease as a model for genetic risk disclosure: implications for personal genomics. Clin. Genet. 80:407–14
    [Google Scholar]
  93. 93.
    Roberts JS, Green RC 2021. Disclosing APOE genotype to individuals at risk for Alzheimer's disease. In World Alzheimer Report 2021: Journey Through the Diagnosis of Dementia S Gauthier, P Rosa-Neto, JA Morais, C Webster 179–81. London: Alzheimer's Dis. Int. https://www.genomes2people.org/wp-content/uploads/2021/09/20210930_AlzheimersDiseaseInternational_Roberts_WorldAlzheimerReport2021.pdf
    [Google Scholar]
  94. 94.
    Robinson JO, Wynn J, Biesecker B, Biesecker L, Bernhardt B et al. 2019. Psychological outcomes related to exome and genome sequencing result disclosure: a meta-analysis of seven Clinical Sequencing Exploratory Research (CSER) Consortium studies. Genet. Med. 21:2781–90
    [Google Scholar]
  95. 95.
    Rothstein MA. 2012. Disclosing decedents’ research results to relatives violates the HIPAA privacy rule. Am. J. Bioeth. 12:116–17
    [Google Scholar]
  96. 96.
    Rothstein MA. 2018. GINA at ten and the future of genetic nondiscrimination law. Hastings Cent. Rep. 48:35–7
    [Google Scholar]
  97. 97.
    Rothstein MA. 2021. Can genetic nondiscrimination laws save lives?. Hastings Cent. Rep. 51:16–7
    [Google Scholar]
  98. 98.
    SACHRP (Secr. Advis. Comm. Hum. Res. Prot.) 2015. Attachment C: return of individual results and special consideration of issues arising from amendments of HIPAA and CLIA. US Department of Health and Human Services https://www.hhs.gov/ohrp/sachrp-committee/recommendations/2015-september-28-attachment-c
    [Google Scholar]
  99. 99.
    SACHRP (Secr. Advis. Comm. Hum. Res. Prot.) 2016. Attachment B: return of individual research results. US Department of Health and Human Services https://www.hhs.gov/ohrp/sachrp-committee/recommendations/attachment-b-return-individual-research-results
    [Google Scholar]
  100. 100.
    Sanderson SC, Linderman MD, Suckiel SA, Zinberg R, Wasserstein M et al. 2017. Psychological and behavioural impact of returning personal results from whole-genome sequencing: the HealthSeq project. Eur. J. Hum. Genet. 25:280–92
    [Google Scholar]
  101. 101.
    Sayeed S, Califf R, Green R, Wong C, Mahaffey K et al. 2021. Return of individual research results: What do participants prefer and expect?. PLOS ONE 16:e0254153
    [Google Scholar]
  102. 102.
    Scherr CL, Aufox S, Ross AA, Ramesh S, Wicklund CA, Smith M. 2018. What people want to know about their genes: a critical review of the literature on large-scale genome sequencing studies. Healthcare 6:96
    [Google Scholar]
  103. 103.
    Schupmann W, Miner SA, Sullivan HK, Glover JR, Hall JE et al. 2021. Exploring the motivations of research participants who chose not to learn medically actionable secondary genetic findings about themselves. Genet. Med. 23:2281–88
    [Google Scholar]
  104. 104.
    Streeten EA, See VY, Jeng LBJ, Maloney KA, Lynch M et al. 2020. KCNQ1 and long QT syndrome in 1/45 Amish: the road from identification to implementation of culturally appropriate precision medicine. Circ. Genom. Precis. Med. 13:e003133
    [Google Scholar]
  105. 105.
    Sullivan HK, Berkman BE. 2018. Incidental findings in low-resource settings. Hastings Cent. Rep. 48:320–28
    [Google Scholar]
  106. 106.
    Tabor HK, Berkman BE, Hull SC, Bamshad MJ. 2011. Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. Am. J. Med. Genet. A 155:2916–24
    [Google Scholar]
  107. 107.
    Taliun D, Harris DN, Kessler MD, Carlson J, Szpiech ZA et al. 2021. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed program. Nature 590:290–99
    [Google Scholar]
  108. 108.
    Terry SF. 2012. The tension between policy and practice in returning research results and incidental findings in genomic biobank research. Minn. J. Law Sci. Technol. 13:691–736
    [Google Scholar]
  109. 109.
    Thorogood A, Bobe J, Prainsack B, Middleton A, Scott E et al.(Particip. Values Task Team Glob. Alliance Genom. Health) 2018. APPLaUD: access for patients and participants to individual level uninterpreted genomic data. Hum. Genom. 12:7
    [Google Scholar]
  110. 110.
    Thorogood A, Dalpé G, Knoppers BM. 2019. Return of individual genomic research results: Are laws and policies keeping step?. Eur. J. Hum. Genet. 27:535–46
    [Google Scholar]
  111. 111.
    UK Biobank 2022. Whole genome sequencing: transforming health research FAQ Doc., UK Biobank Stockport, UK: https://www.ukbiobank.ac.uk/media/i2phrjfz/wgs-faq-final-at.pdf
    [Google Scholar]
  112. 112.
    Vears DF, Minion JT, Roberts SJ, Cummings J, Machirori M et al. 2021. Return of individual research results from genomic research: a systematic review of stakeholder perspectives. PLOS ONE 16:e0258646
    [Google Scholar]
  113. 113.
    Venner E, Muzny D, Smith JD, Walker K, Neben CL et al. 2022. Whole-genome sequencing as an investigational device for return of hereditary disease risk and pharmacogenomic results as part of the All of Us Research Program. Genome Med. 14:34
    [Google Scholar]
  114. 114.
    Wiesner GL, Kulchak Rahm A, Appelbaum P, Aufox S, Bland ST et al. 2020. Returning results in the genomic era: initial experiences of the eMERGE network. J. Pers. Med. 10:30
    [Google Scholar]
  115. 115.
    Wilfond BS, Kauffman TL, Jarvik GP, Reiss JA, Richards CS et al. 2018. Lessons learned from a study of genomics-based carrier screening for reproductive decision making. Health Affairs 37:809–16
    [Google Scholar]
  116. 116.
    Wolf SM. 2013. Return of individual research results and incidental findings: facing the challenges of translational science. Annu. Rev. Genom. Hum. Genet. 14:557–77
    [Google Scholar]
  117. 117.
    Wolf SM, Amendola LM, Berg JS, Chung WK, Clayton EW et al. 2018. Navigating the research-clinical interface in genomic medicine: analysis from the CSER Consortium. Genet. Med. 20:545–53
    [Google Scholar]
  118. 118.
    Wolf SM, Branum R, Koenig BA, Petersen GM, Berry SA et al. 2015. Returning a research participant's genomic results to relatives: analysis and recommendations. J. Law Med. Ethics 43:440–63
    [Google Scholar]
  119. 119.
    Wolf SM, Burke W, Koenig BA. 2015. Mapping the ethics of translational genomics: situating return of results and navigating the research-clinical divide. J. Law Med. Ethics 43:486–501
    [Google Scholar]
  120. 120.
    Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP et al. 2012. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet. Med. 14:361–84
    [Google Scholar]
  121. 121.
    Wolf SM, Evans BJ. 2018. Return of results and data to study participants. Science 362:159–60
    [Google Scholar]
  122. 122.
    Wolf SM, Evans BJ. 2019. Defending the return of results and data. Science 362:1255–56
    [Google Scholar]
  123. 123.
    Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK et al. 2008. Managing incidental findings in human subjects research: analysis and recommendations. J. Law Med. Ethics 36:219–48
    [Google Scholar]
  124. 124.
    Wolf SM, Paradise J, Caga-Anan C. 2008. The law of incidental findings in human subjects research: establishing researchers’ duties. J. Law Med. Ethics 36:361–83
    [Google Scholar]
  125. 125.
    Wolf SM, Scholtes E, Koenig BA, Petersen GM, Berry SA et al. 2018. Pragmatic tools for sharing genomic research results with the relatives of living and deceased research participants. J. Law Med. Ethics 46:87–109
    [Google Scholar]
  126. 126.
    Wright CF, Middleton A, Barrett JC, Firth HV, FitzPatrick DR et al. 2017. Returning genome sequences to research participants: policy and practice. Wellcome Open Res. 2:15
    [Google Scholar]
  127. 127.
    Wright MF, Lewis KL, Fisher TC, Hooker GW, Emanuel TE et al. 2014. Preferences for results delivery from exome sequencing/genome sequencing. Genet. Med. 16:442–47
    [Google Scholar]
  128. 128.
    Yu JH, Crouch J, Jamal SM, Tabor HK, Bamshad MJ. 2013. Attitudes of African Americans toward return of results from exome and whole genome sequencing. Am. J. Med. Genet. A 161:1064–72
    [Google Scholar]
  129. 129.
    Zawatsky CLB, Shah N, Machini K, Perez E, Christensen KD et al. 2021. Returning actionable genomic results in a research biobank: analytic validity, clinical implementation and resource utilization. Am. J. Hum. Genet. 108:2224–37
    [Google Scholar]
/content/journals/10.1146/annurev-genom-101122-103209
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