Proposals to return medically actionable secondary genetic findings (SFs) in the clinical and research settings have generated controversy regarding whether to solicit individuals’ preferences about their “right not to know” genetic information. This study contributes to the debate by surveying research participants who have actively decided whether to accept or refuse SFs.
Participants were drawn from a large National Institutes of Health (NIH) environmental health study. Participants who had accepted SFs (n = 148) or refused SFs (n = 83) were given more detailed information about the types of SFs researchers could return and were given an opportunity to revise their original decision.
Forty-one of 83 initial refusers (49.4%) opted to receive SFs following the informational intervention. Nearly 75% of these “reversible refusers” thought they had originally accepted SFs. The 50.6% of initial refusers who continued to refuse (“persistent refusers”) demonstrated high levels of understanding of which SFs would be returned postintervention. The most prominent reason for refusing was concern about becoming worried or sad (43.8%).
This study demonstrates the need for a more robust informed consent process when soliciting research participants’ preferences about receiving SFs. We also suggest that our data support implementing a default practice of returning SFs without actively soliciting preferences.
Subscribe to Journal
Get full journal access for 1 year
We are sorry, but there is no personal subscription option available for your country.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Data is available upon individual request.
Presidential Commission for the Study of Bioethical Issues. Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings in the Clinical, Research, and Direct-to-Consumer Contexts. Washington, DC: 2013.
Green RC, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013;15:565–74.
Miller DT, et al. 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. 2021. https://doi.org/10.1038/s41436-021-01172-3. Online ahead of print.
Berkman BE. Refuting the right not to know. J Health Care Law Policy. 2017;19:1–75.
Burke W, et al. Recommendations for returning genomic incidental findings? We need to talk! Genet Med. 2013;15:854–9.
Wolf SM, Annas GJ, Elias S. Patient autonomy and incidental findings in clinical genomics. Science. 2013;340:1049–50.
Ross LF, Rothstein MA, Clayton EW. Mandatory extended searches in all genome sequencing: “incidental findings,” patient autonomy, and shared decision making. JAMA. 2013;310:367.
Klitzman R, Appelbaum PS, Chung W. Return of secondary genomic findings vs patient autonomy: implications for medical care. JAMA. 2013;310:369.
Holtzman NA. ACMG recommendations on incidental findings are flawed scientifically and ethically. Genet Med. 2013;15:750–1.
Allyse M, Michie M. Not-so-incidental findings: the ACMG recommendations on the reporting of incidental findings in clinical whole genome and whole exome sequencing. Trends Biotechnol. 2013;31:439–41.
Townsend A, Adam S, Birch PH, Friedman JM. Paternalism and the ACMG recommendations on genomic incidental findings: patients seen but not heard. Genet Med. 2013;15:751–2.
Gliwa C, Yurkiewicz IR, Lehmann LS, Hull SC, Jones N, Berkman BE. Institutional review board perspectives on obligations to disclose genetic incidental findings to research participants. Genet Med. 2016;18:705–11.
American College of Medical Genetics and Genomics. ACMG updates recommendation on “opt out” for genome sequencing return of results. 2014. https://www.acmg.net/docs/Release_ACMGUpdatesRecommendations_final.pdf.
Mandava A, Pace C, Campbell B, Emanuel E, Grady C. The quality of informed consent: mapping the landscape. A review of empirical data from developing and developed countries. J Med Ethics. 2012;38:356–65.
Gong J, Zhang Y, Yang Z, Huang Y, Feng J, Zhang W. The framing effect in medical decision-making: a review of the literature. Psychol Health Med. 2013;18:645–53.
Jamal L, et al. When bins blur: patient perspectives on categories of results from clinical whole genome sequencing. AJOB Empir Bioeth. 2017;8:82–8.
Wynn J, et al. Research participants’ preferences for hypothetical secondary results from genomic research. J Genet Couns. 2017;26:841–51.
Bennette CS, et al. Return of incidental findings in genomic medicine: measuring what patients value—development of an instrument to measure preferences for information from next-generation testing (IMPRINT). Genet Med. 2013;15:873–81.
Vornanen M, Aktan-Collan K, Hallowell N, Konttinen H, Haukkala A. Lay perspectives on receiving different types of genomic secondary findings: a qualitative vignette study. J Genet Couns. 2019;28:343–54.
Hoell C, et al. Participant choices for return of genomic results in the eMERGE Network. Genet Med. 2020;22:1821–29.
Chulada PC, et al. The Environmental Polymorphism Registry: a DNA resource to study genetic susceptibility loci. Hum Genet. 2008;123:207–14.
Middleton A, Bragin E, Firth HV, Hurles ME, Wright CF, Parker M. Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research. Eur J Hum Genet. 2016;24:21–9.
Wright MF, et al. Preferences for results delivery from exome sequencing/genome sequencing. Genet Med. 2014;16:442–7.
Kaufman D, Murphy J, Scott J, Hudson K. Subjects matter: a survey of public opinions about a large genetic cohort study. Genet Med. 2008;10:831–9.
Bollinger JM, Scott J, Dvoskin R, Kaufman D. Public preferences regarding the return of individual genetic research results: findings from a qualitative focus group study. Genet Med. 2012;14:451–7.
Shahmirzadi L, Chao EC, Palmaer E, Parra MC, Tang S, Gonzalez KDF. Patient decisions for disclosure of secondary findings among the first 200 individuals undergoing clinical diagnostic exome sequencing. Genet Med. 2014;16:395–9.
Facio FM, et al. Intentions to receive individual results from whole-genome sequencing among participants in the ClinSeq study. Eur J Hum Genet. 2013;21:261–5.
Morren M, Rijken M, Baanders AN, Bensing J. Perceived genetic knowledge, attitudes towards genetic testing, and the relationship between these among patients with a chronic disease. Patient Educ Couns. 2007;65:197–4.
Henneman L, Timmermans DRM, Wal GVD. Public attitudes toward genetic testing: perceived benefits and objections. Genet Test. 2006;10:139–45.
Halverson CME, Wessinger BC, Clayton EW, Wiesner GL. Patients’ willingness to reconsider cancer genetic testing after initially declining: Mention it again. J Genet Couns. 2020;29:18–24.
Parens E, Appelbaum PS. On what we have learned and still need to learn about the psychosocial impacts of genetic testing. Hastings Center Report. 2019;49:S2–9.
Wilson TD, Gilbert DT. Affective forecasting: knowing what to want. Curr Dir Psychol Sci. 2005;14:131–4.
Prince AE, Berkman BE. Reconceptualizing harms and benefits in the genomic age. Per Med. 2018;15:419–28.
National Human Genome Research Institute. Genetic discrimination. https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination. Accessed 3 June 2020.
Rothstein MA. Putting the Genetic Information Nondiscrimination Act in context. Genet Med. 2008;10:655–6.
Bortolotti L, Widdows H. The right not to know: the case of psychiatric disorders. J Med Ethics. 2011;37:673–6.
Armstrong K. Racial differences in the use of BRCA1/2 testing among momen with a family history of breast or ovarian cancer. JAMA. 2005;293:1729.
Moorman PG, Skinner C, Evans JP, Newman B, Sorenson JR. Racial differences in enrolment in a cancer genetics registry. Cancer Epidemiol Biomarkers Prev. 2004;13:1349–54.
Peters N, Rose A, Armstrong K. The association between race and attitudes about predictive genetic testing. Cancer Epidemiol Biomarkers Prev. 2004;13:361–5.
Bussey-Jones J, Garrett J, Henderson G, Moloney M, Blumenthal C, Corbie-Smith G. The role of race and trust in tissue/blood donation for genetic research. Genet Med. 2010;12:116–21.
We thank Sara Chandros Hull, Holly Taylor, and Leila Jamal for their review, as well as the Department of Bioethics at the NIH Clinical Center, and Fikri Yucel, Social and Scientific Systems, for assistance with the study.
This research was supported by the Intramural Research Program of the National Institutes of Health, including funding from the National Human Genome Research Institute, the National Institute of Environmental Health Sciences, and the NIH Clinical Center.
The EPR (Protocol 04-E-0053, Clinicaltrials.gov NCT00341237) and this substudy were approved by the NIH IRB. Informed consent was obtained from all participants as required by the IRB. Individual level data was de-identified.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The views expressed are the authors’ own. They do not represent the position or policy of the National Institutes of Health, U.S. Public Health Service, or the Department of Health and Human Services.
About this article
Cite this article
Schupmann, W., Miner, S.A., Sullivan, H.K. et al. Exploring the motivations of research participants who chose not to learn medically actionable secondary genetic findings about themselves. Genet Med (2021). https://doi.org/10.1038/s41436-021-01271-1