Abstract
The return of individual genomic results (ROR) to research participants is still in its early phase, and insight on how individuals respond to ROR is scarce. Studies contributing to the evidence base for best practices are crucial before these can be established. Here, we describe a ROR procedure conducted at a population-based biobank, followed by surveying the responses of almost 3000 participants to a range of results, and discuss lessons learned from the process, with the aim of facilitating large-scale expansion. Overall, participants perceived the information that they received with counseling as valuable, even when the reporting of high risks initially caused worry. The face-to-face delivery of results limited the number of participants who received results. Although the participants highly valued this type of communication, additional means of communication need to be considered to improve the feasibility of large-scale ROR. The feedback collected sheds light on the value judgements of the participants and on potential responses to the receipt of genetic risk information. Biobanks in other countries are planning or conducting similar projects, and the sharing of lessons learned may provide valuable insight and aid such endeavors.
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Data availability
Data mentioned in the paper can be found within the published article and its supplementary files, and additional data generated or analysed during this study are available from the corresponding author upon reasonable request.
References
de Wert G, Dondorp W, Clarke A, Dequeker EMC, Cordier C, Deans Z, et al. Opportunistic genomic screening. Recommendations of the European Society of Human Genetics. Eur J Hum Genet. 2021;29:365–77.
Lewis ACF, Knoppers BM, Green RC. An international policy on returning genomic research results. Genome Med. 2021;13:115.
Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, et al. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008;36:219–48.
Budin-ljøsne I, Mascalzoni D, Soini S, Machado H, Kaye J, Bentzen HB, et al. Feedback of individual genetic results to research participants: is it feasible in Europe? Biopreserv Biobank. 2016;14:241–8.
West KM, Blacksher E, Cavanaugh KL, Fullerton SM, Umeukeje EM, Young BA, et al. At the research-clinical interface: returning individual genetic results to research participants. Clin J Am Soc Nephrol. 2020;15:1181–9.
Middleton A, Morley KI, Bragin E, Firth HV, Hurles ME, Wright CF, et al. Attitudes of nearly 7000 health professionals, genomic researchers and publics toward the return of incidental results from sequencing research. Eur J Hum Genet. 2015;24:1–9.
Vears DF, Minion JT, Roberts SJ, Cummings J, Machirori M, Blell M, et al. Return of individual research results from genomic research: a systematic review of stakeholder perspectives. Plos One. 2021;16:e0258646.
Wilkins CH, Mapes BM, Jerome RN, Villalta-Gil V, Pulley JM, Harris PA. Understanding what information is valued by research participants, and why. Health Aff. 2019;38:399–407.
Facio FM, Brooks S, Loewenstein J, Green S, Biesecker LG, Biesecker BB. Motivators for participation in a whole-genome sequencing study: implications for translational genomics research. Eur J Hum Genet. 2011;19:1213–7.
Mcguire AL, Majumder MA, Villanueva AG, Bardill J, Juli M, Boerwinkle E, et al. Importance of participant-centricity and trust for a sustainable medical information commons. J Law Med Ethics. 2019;47:12–20.
Botkin JR, Mancher M, Busta ER, Downey AS. Returning individual research results to participants: guidance for a new research paradigm. Washington, DC: The National Academies Press; 2018.
Milne R, Morley KI, Almarri MA, Atutornu J, Baranova EE, Bevan P, et al. Return of genomic results does not motivate intent to participate in research for all: perspectives across 22 countries. Genet Med. 2022;24:1120–9.
Sotsiaalministeerium. Eesti elanike teadmised, hoiakud, kartused ja ootused personaalmeditsiini osas Uuringuaruanne Kevad 2015 [Internet]. Sotsiaalministeerium. 2015. Available from: http://sm.ee/et/personaalmeditsiini-juhtprojekti-eeluuring.
Alver M, Palover M, Saar A, Läll K, Zekavat SM, Tõnisson N, et al. Recall by genotype and cascade screening for familial hypercholesterolemia in a population-based biobank from Estonia. Genet Med. 2018;21:1173–80.
Leitsalu L, Palover M, Sikka TT, Reigo A, Kals M, Parn K, et al. Genotype-first approach to the detection of hereditary breast and ovarian cancer risk, and effects of risk disclosure to biobank participants. Eur J Hum Genet. 2021;29:471–81.
Leitsalu L, Alavere H, Jacquemont S, Kolk A, Maillard AM, Reigo A, et al. Reporting incidental findings of genomic disorder-associated copy number variants to unselected biobank participants. Per Med. 2016;13:303–14.
Haukkala A, Kujala E, Alha P, Salomaa V, Koskinen S, Swan H, et al. The return of unexpected research results in a biobank study and referral to health care for heritable long QT syndrome. Public Health Genomics. 2013;16:241–50.
Blout Zawatsky CL, Shah N, Machini K, Perez E, Christensen KD, Zouk H, et al. Returning actionable genomic results in a research biobank: analytic validity, clinical implementation, and resource utilization. Am J Hum Genet. 2021;12:2224–37.
Leitsalu L, Haller T, Esko T, Tammesoo M-L, Alavere H, Snieder H, et al. Cohort profile: Estonian biobank of the Estonian genome center, university of Tartu. Int J Epidemiol. 2015;44:1137–47.
Riigikogu. Human Genes Research Act [Internet]. 2000 [cited 2014 Jun 27]. Available from: https://www.riigiteataja.ee/en/eli/531102013003/consolide.
Leitsalu L, Alavere H, Tammesoo M, Leego E, Metspalu A. Linking a population biobank with national health registries — The Estonian experience. J Pers Med. 2015;5:96–106.
Läll K, Mägi R, Morris A, Metspalu A, Fischer K. Personalized risk prediction for type 2 diabetes: the potential of genetic risk scores. Genet Med. 2017;19:322–9.
Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44:981–90.
Abraham G, Havulinna AS, Bhalala OG, Byars SG, De Livera AM, Yetukuri L, et al. Genomic prediction of coronary heart disease. Eur Heart J. 2016;37:3267–78.
Day FR, Ruth KS, Thompson DJ, Lunetta KL, Pervjakova N, Chasman DI, et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet. 2015;47:1294–303.
Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. ACMG Statement 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 Genomics. Genet Med. 2017;19:249–55.
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46:D1062–7.
Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:434–43.
Reisberg S, Krebs K, Lepamets M, Kals M, Mägi R, Metsalu K, et al. Translating genotype data of 44,000 biobank participants into clinical pharmacogenetic recommendations: challenges and solutions. Genet Med. 2019;21:1245–54.
Barbarino JM, Whirl-Carrillo M, Altman RB, Klein TE. PharmGKB: a worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018;10:e1417.
Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharm Ther. 2011;89:464–7.
Gray SW, Martins Y, Feuerman LZ, Bernhardt BA, Biesecker BB, Christensen KD, et al. Social and behavioral research in genomic sequencing: approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group. Genet Med. 2014;16:727–35.
Marteau TM, Bekker H. The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI). Br J Clin Psychol. 1992;31:301–6.
Brehaut JC, O’Connor AM, Wood TJ, Hack TF, Siminoff L, Gordon E, et al. Validation of a decision regret scale. Med Decis Mak. 2003;23:281–92.
Ormond KE, Hallquist MLG, Buchanan AH, Dondanville D, Cho MK, Smith M. Developing a conceptual, reproducible, Rubric-based approach to consent and result disclosure for genetic testing by clinicians with minimal genetics background. Genet Med. 2019;21:727–35.
Bombard Y, Hayeems RZ. How digital tools can advance quality and equity in genomic medicine. Nat Rev Genet. 2020;21:505–6.
Widén E, Junna N, Ruotsalainen S, Surakka I, Mars N, Ripatti P, et al. How Communicating Polygenic and Clinical Risk for Atherosclerotic Cardiovascular Disease Impacts Health Behavior: an Observational Follow-up Study. Circ Genom Precis Med. 2022;15:e003459.
Funding
This research was supported by the European Union through the European Regional Development Fund (project no. 2014-2020.4.01.15-0012 and SLTAT16148T/TK148) and by Personal Research Funding grants from the Estonian Research Council (PRG555, PRG1095, PRG184, PRG1197).
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(CRediT statements). LL: Conceptualization, Formal analysis, Investigation, Writing - Original Draft, Visualization. AR: Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualization, Project administration. MP: Methodology, Investigation. TN: Methodology, Validation, Writing - Review & Editing. KL: Methodology. KK: Methodology. SR: Methodology. RM: Methodology. MK: Methodology. HA: Methodology, Investigation, Project administration. MN: Investigation, Writing - Review & Editing. AK: Investigation. IN: Investigation. MLT: Data Curation. EK: Formal analysis. MP: Methodology, Software. KM: Methodology, Software. AA: Methodology, Project administration. LM: Methodology, Writing - Review & Editing, Supervision, Funding acquisition. KF: Methodology, Formal analysis, Visualization, Writing - Review & Editing, Supervision, Funding acquisition. NT: Conceptualization, Methodology, Formal analysis, Investigation, Resources, Writing - Review & Editing, Supervision, Funding acquisition. AM: Conceptualization, Resources, Writing - Review & Editing, Supervision, Funding acquisition.
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The authors declare no competing interests.
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The ROR procedure, from registration to feedback collection, including the informed consent procedure, was approved by the ethics committee of the University of Tartu (no. 271/T-22). Informed consent was obtained from all participants as required by the REC. The biobank has been described previously [19] and more details about the biobank can be found at the biobank’s website https://genomics.ut.ee/en/content/estonian-biobank.
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Leitsalu, L., Reigo, A., Palover, M. et al. Lessons learned during the process of reporting individual genomic results to participants of a population-based biobank. Eur J Hum Genet 31, 1048–1056 (2023). https://doi.org/10.1038/s41431-022-01196-6
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DOI: https://doi.org/10.1038/s41431-022-01196-6