Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Polygenic risk scores in the clinic: a systematic review of stakeholders’ perspectives, attitudes, and experiences

European Journal of Human Genetics volume 33, pages 266–280 (2025) Cite this article

Subjects

Abstract

Polygenic Risk Scores (PRS) are statistical methods estimating part of an individual’s genetic susceptibility to various disease phenotypes. Their potential clinical applications to enhance the prediction, prevention, and risk management of complex conditions motivate current research efforts worldwide. While a growing body of literature has highlighted the scientific and ethical limitations of PRS, the technology’s clinical translation will present both opportunities and challenges for the stakeholders involved. Here, a mixed-method systematic review of empirical studies was performed to gather evidence on the perspectives, attitudes, and experiences of healthcare providers, patients, and the public regarding the use of PRS in healthcare settings. The PRISMA reporting protocol was followed and 24 articles were included. Three major themes were identified. First, we reported on participants’ familiarity with the test, including their knowledge, understanding, and education on PRS’ clinical use. The second theme collects stakeholders’ motivations for taking the test and their perspectives on sensitive issues related to the return of results. Participants’ normative stances regarding the appropriate use of PRS, their benefits, and harms were presented in the third theme. The findings underscore significant knowledge gaps and challenges in the clinical interpretation of PRS among healthcare providers. On the other hand, the provision of genetic counseling benefitted patients’ understanding of PRS results and in most cases, no psychosocial burden was reported. Finally, the review highlights that stakeholders’ perspectives on the clinical use of PRS are highly context-dependent, shaped by population characteristics, disease type, and social factors, emphasizing the need for tailored approaches across diverse healthcare settings.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
The alternative text for this image may have been generated using AI.
Fig. 2
The alternative text for this image may have been generated using AI.
Fig. 3
The alternative text for this image may have been generated using AI.
Fig. 4
The alternative text for this image may have been generated using AI.

Similar content being viewed by others

Data availability

The data generated and analyzed during the review are included in the article and its supplements.

References

  1. Truong B, Hull LE, Ruan Y, Huang QQ, Hornsby W, Martin H, et al. Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases. medRxiv. 2023;2023.02.21.23286110.

  2. Purcell SM, Wray NR, Stone JL, Visscher PM, O’Donovan MC, Sullivan PF, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460:748–52.

    CAS  PubMed  Google Scholar 

  3. Uffelmann E, Huang QQ, Munung NS, de Vries J, Okada Y, Martin AR, et al. Genome-wide association studies. Nat Rev Methods Primer [Internet]. 2021;1. Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85130483314&doi=10.1038%2fs43586-021-00056-9&partnerID=40&md5=76ec5878ffa006b27b2493ec9b01c27f.

  4. Cleynen I, Halfvarsson J. How to approach understanding complex trait genetics – inflammatory bowel disease as a model complex trait. U Eur Gastroenterol J. 2019;7:1426–30.

    CAS  Google Scholar 

  5. Lilyquist J, Ruddy KJ, Vachon CM, Couch FJ. Common genetic variation and breast cancer risk - past, present, and future. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2018;27:380–94.

    CAS  Google Scholar 

  6. Slunecka JL, van der Zee MD, Beck JJ, Johnson BN, Finnicum CT, Pool R, et al. Implementation and implications for polygenic risk scores in healthcare. Hum Genomics. 2021;15:46.

    PubMed  PubMed Central  Google Scholar 

  7. Fritzsche MC, Akyüz K, Cano Abadía M, McLennan S, Marttinen P, Mayrhofer MTH, et al. Ethical layering in AI-driven polygenic risk scores—New complexities, new challenges. Front Genet [Internet]. 2023 [cited 2023 Aug 15];14. Available from: https://www.frontiersin.org/articles/10.3389/fgene.2023.1098439.

  8. Choi SW, Mak TSH, O’Reilly PF. A guide to performing polygenic risk score analyses. Nat Protoc. 2020;15:2759–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Mabey B, Hughes E, Kucera M, Simmons T, Hullinger B, Pederson HJ, et al. Validation of a clinical breast cancer risk assessment tool combining a polygenic score for all ancestries with traditional risk factors. Genet Med. 2024;26:101128.

  10. WISDOM Study [Internet]. [cited 2024 Jul 2]. The WISDOM Study - Join The Movement. Available from: https://www.thewisdomstudy.org/.

  11. Electronic Medical Records and Genomics (eMERGE) Network [Internet]. [cited 2024 Jul 2]. Available from: https://www.cgm.northwestern.edu/research/emerge-network/index.html.

  12. Our Future Health supports Genome UK Implementation Plan for England – Our Future Health [Internet]. [cited 2024 Jul 2]. Available from: https://ourfuturehealth.org.uk/news/our-future-health-supports-genome-uk-implementation-plan-for-england/.

  13. Andreoli L, Peeters H, Van Steen K, Dierickx K. Taking the risk. A systematic review of ethical reasons and moral arguments in the clinical use of polygenic risk scores. Am J Med Genet A. 2024;194:e63584.

  14. Eeltink E, van der Horst MZ, Zinkstok JR, Aalfs CM, Luykx JJ. Polygenic risk scores for genetic counseling in psychiatry: lessons learned from other fields of medicine. Neurosci Biobehav Rev. 2021;121:119–27.

    CAS  PubMed  Google Scholar 

  15. Knoppers BM, Bernier A, Granados Moreno P, Pashayan N. Of screening, stratification, and scores. J Pers Med. 2021;11:736.

    PubMed  PubMed Central  Google Scholar 

  16. Sud A, Horton RH, Hingorani AD, Tzoulaki I, Turnbull C, Houlston RS, et al. Realistic expectations are key to realising the benefits of polygenic scores. BMJ. 2023;380:e073149.

    PubMed  PubMed Central  Google Scholar 

  17. Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3:77–101.

    Google Scholar 

  18. Martin A, Kanai M, Kamatani Y, Okada Y, Neale B, Daly M. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet. 2019;51:584–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Lewis ACF, Green RC. Polygenic risk scores in the clinic: new perspectives needed on familiar ethical issues. Genome Med. 2021;13:14.

    PubMed  PubMed Central  Google Scholar 

  20. Abu-El-Haija A, Reddi HV, Wand H, Rose NC, Mori M, Qian E, et al. The clinical application of polygenic risk scores: a points to consider statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023;25:100803.

    CAS  PubMed  Google Scholar 

  21. Young MA, Yanes T, Cust AE, Dunlop K, Limb S, Newson AJ, et al. Human genetics society of Australasia position statement: use of polygenic scores in clinical practice and population health. Twin Res Hum Genet. 2023;26:40–8.

    PubMed  Google Scholar 

  22. O’Sullivan JW, Raghavan S, Marquez-Luna C, Luzum JA, Damrauer SM, Ashley EA, et al. Polygenic risk scores for cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2022;146:E93–118.

    PubMed  PubMed Central  Google Scholar 

  23. Group BMJP. Accountability for reasonableness: establishing a fair process for priority setting is easier than agreeing on principles. BMJ. 2000;321:1300–1. Nov 25

    Google Scholar 

  24. Stern C, Lizarondo L, Carrier J, Godfrey C, Rieger K, Salmond S, et al. Methodological guidance for the conduct of mixed methods systematic reviews. JBI Evid Synth. 2020;18:2108–18.

    PubMed  Google Scholar 

  25. JBI Manual for Evidence Synthesis - JBI Global Wiki [Internet]. [cited 2024 Apr 29]. Available from: https://jbi-global-wiki.refined.site/space/MANUAL.

  26. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLOS Med. 2009;6:e1000100.

    PubMed  PubMed Central  Google Scholar 

  27. Johnson N, Phillips M. Rayyan for systematic reviews. J Electron Resour Librariansh. 2018;30:46–8.

    Google Scholar 

  28. Hong QN, Fàbregues S, Bartlett G, Boardman F, Cargo M, Dagenais P, et al. The mixed methods appraisal tool (MMAT) version 2018 for information professionals and researchers. Educ Inf. 2018;34:285–91.

    Google Scholar 

  29. Heyvaert M, Hannes K, Onghena P. Using mixed methods research synthesis for literature reviews: the mixed methods research synthesis approach. SAGE Publications; 2016. 345.

  30. Braun V, Clarke V. One size fits all? What counts as quality practice in (reflexive) thematic analysis? Qual Res Psychol. 2021;18:328–52.

    Google Scholar 

  31. Smit AK, Sharman AR, Espinoza D, Wallingford C, Young MA, Dunlop K, et al. Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: A cross-sectional survey of health professionals. Clin Genet. 2021;100:430–9.

    CAS  PubMed  Google Scholar 

  32. Pereira S, Munoz KA, Small BJ, Soda T, Torgerson LN, Sanchez CE, et al. Psychiatric polygenic risk scores: {Child} and adolescent psychiatrists’ knowledge, attitudes, and experiences. Am J Med Genet PART B-Neuropsychiatr Genet 2022;189:293–302.

    Google Scholar 

  33. Lewis ACF, Perez EF, Prince AER, Flaxman HR, Gomez L, Brockman DG, et al. Patient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization. Genome Med. 2022;14:114.

    PubMed  PubMed Central  Google Scholar 

  34. Riddle L, Joseph G, Caruncho M, Koenig BA, James JE. The role of polygenic risk scores in breast cancer risk perception and decision-making. J Community Genet. 2023;14:489–501.

    PubMed  PubMed Central  Google Scholar 

  35. Yanes T, Kaur R, Meiser B, Scheepers-Joynt M, McInerny S, Barlow-Stewart K, et al. Women’s responses and understanding of polygenic breast cancer risk information. Fam Cancer. 2020;19:297–306.

    CAS  PubMed  Google Scholar 

  36. Young MA, Forrest LE, Rasmussen VM, James P, Mitchell G, Sawyer SD, et al. Making sense of SNPs: women’s understanding and experiences of receiving a personalized profile of their breast cancer risks. J Genet Couns. 2018;27:702–8.

    PubMed  Google Scholar 

  37. Laza-Vásquez C, Martínez-Alonso M, Forné-Izquierdo C, Vilaplana-Mayoral J, Cruz-Esteve I, Sánchez-López I, et al. Feasibility and acceptability of personalized breast cancer screening (DECIDO study): a single-arm proof-of-concept trial. Int J Environ Res Public Health [Internet]. 2022 [cited 8AD Jan 1];19. Available from: https://pubmed.ncbi.nlm.nih.gov/36012059/.

  38. Willis AM, Smith SK, Meiser B, James PA, Ballinger ML, Thomas DM, et al. Influence of lived experience on risk perception among women who received a breast cancer polygenic risk score: “Another piece of the pie”. J Genet Couns. 2021;30:849–60.

    PubMed  Google Scholar 

  39. Forrest LE, Sawyer SD, Hallowell N, James PA, Young MA. High-risk women’s risk perception after receiving personalized polygenic breast cancer risk information. J Community Genet. 2019;10:197–206.

    PubMed  Google Scholar 

  40. Putt S, Yanes T, Meiser B, Kaur R, Fullerton JM, Barlow-Stewart K, et al. Exploration of experiences with and understanding of polygenic risk scores for bipolar disorder. J Affect Disord. 2020;265:342–50.

    CAS  PubMed  Google Scholar 

  41. Saya S, McIntosh J, Winship I, Milton S, Clendenning M, Kyriakides M, et al. Informed choice and attitudes regarding a genomic test to predict risk of colorectal cancer in general practice. Patient Educ Couns. 2022;105:987–95.

    PubMed  Google Scholar 

  42. Casauria S, Lewis S, Lynch F, Saffery R. Australian parental perceptions of genomic newborn screening for non-communicable diseases. Front Genet. 2023;14:1209762.

    PubMed  PubMed Central  Google Scholar 

  43. Terek S, Del Rosario MC, Hain HS, Connolly JJ, Behr MA, Harr M, et al. Attitudes among parents towards return of disease-related polygenic risk scores (PRS) for their children. J Pers Med. 2022;12:1945.

    PubMed  PubMed Central  Google Scholar 

  44. Suckiel SA, Braganza GT, Aguiñiga KL, Odgis JA, Bonini KE, Kenny EE, et al. Perspectives of diverse Spanish- and English-speaking patients on the clinical use of polygenic risk scores. Genet Med J Am Coll Med Genet. 2022;24:1217–26.

    CAS  Google Scholar 

  45. Kamp M, Pain O, May A, Lewis CM, Ramsay M. Clinicians’ Perceptions towards Precision Medicine Tools for Cardiovascular Disease Risk Stratification in South Africa. J Pers Med. 2022;12:1360.

  46. Ayoub A, Lapointe J, Nabi H, Pashayan N. Risk-stratified breast cancer screening incorporating a polygenic risk score: a survey of UK general practitioners’ knowledge and attitudes. Genes. 2023;14:732.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Lapointe J, Buron AC, Mbuya-Bienge C, Dorval M, Pashayan N, Brooks JD, et al. Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals. Genet Med J Am Coll Med Genet. 2022;24:2380–8.

    CAS  Google Scholar 

  48. Hollitt GL, Siggs OM, Ridge B, Keane MC, Mackey DA, MacGregor S, et al. Attitudes towards polygenic risk testing in individuals with glaucoma. In 2022. p. 436–46. Available from: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123182731&doi=10.1016%2fj.ogla.2021.11.002&partnerID=40&md5=87877dd09be8129d124ca93d70f24d35.

  49. Sierra MA, Wheeler JCW, Devereux L, Trainer AH, Keogh L. Exploring {implementation} of {personal} {breast} {cancer} {risk} {assessments}. J Pers Med. 2021;11.

  50. Pacyna JE, Ennis JS, Kullo IJ, Sharp RR. Examining the {impact} of {polygenic} {risk} {information} in {primary} {care}. J Prim Care Community Health. 2023;14:21501319231151766.

    PubMed  PubMed Central  Google Scholar 

  51. Yanes T, Young MA, Meiser B, James PA. Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field. Breast Cancer Res. 2020;22:21.

    PubMed  PubMed Central  Google Scholar 

  52. Moorthy T, Nguyen H, Chen Y, Austin J, Smoller J, Hercher L, et al. How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia? Am J Med Genet PART B-Neuropsychiatr Genet. 2023;192:161–70.

    Google Scholar 

  53. Vassy JL, Kerman BJ, Harris EJ, Lemke AA, Clayman ML, Antwi AA, et al. Perceived benefits and barriers to implementing precision preventive care: Results of a national physician survey. Eur J Hum Genet EJHG. 2023;31:1309–16.

    PubMed  Google Scholar 

  54. Venning B, Saya S, De Abreu Lourenco R, Street DJ, Emery JD. Preferences for a polygenic test to estimate cancer risk in a general Australian population. Genet Med. 2022;24:2144–54.

    CAS  PubMed  Google Scholar 

  55. Woof VG, McWilliams L, Donnelly LS, Howell A, Evans DG, Maxwell AJ, et al. Introducing a low-risk breast screening pathway into the NHS Breast Screening Programme: Views from healthcare professionals who are delivering risk-stratified screening. Women’s Health Lond Engl. 2021;17:17455065211009746.

    CAS  Google Scholar 

  56. Christensen KD, Vassy JL, Jamal L, Lehmann LS, Slashinski MJ, Perry DL, et al. Are physicians prepared for whole genome sequencing? a qualitative analysis. Clin Genet. 2016;89:228–34.

    CAS  PubMed  Google Scholar 

  57. Nisselle A, King E, Terrill B, Davey B, McClaren B, Dunlop K, et al. Investigating genomic medicine practice and perceptions amongst Australian non-genetics physicians to inform education and implementation. NPJ Genom Med. 2023;8:13.

    PubMed  PubMed Central  Google Scholar 

  58. Siermann M, Phillips A, Claesen-Bengtson Z, Steijvoort EV Stimulating professional collective responsibility from the outset in mainstreaming genomics. J Med Ethics [Internet]. 2024 May 7 [cited 2024 May 29]; Available from: https://jme-bmj-com.kuleuven.e-bronnen.be/content/early/2024/05/07/jme-2024-109998.

  59. Ha VTD, Frizzo-Barker J, Chow-White P. Adopting clinical genomics: a systematic review of genomic literacy among physicians in cancer care. BMC Med Genomics. 2018;11:18.

    PubMed  PubMed Central  Google Scholar 

  60. Oliveri S, Ferrari F, Manfrinati A, Pravettoni G. A systematic review of the psychological implications of genetic testing: a comparative analysis among cardiovascular, neurodegenerative and cancer diseases. Front Genet. 2018;9:624.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Wade CH. What is the psychosocial impact of providing genetic and genomic health information to individuals? an overview of systematic reviews. Hastings Cent Rep. 2019;49:S88–96.

    PubMed  Google Scholar 

  62. Lowes K, Borle K, Folkersen L, Austin J. A qualitative study exploring the consumer experience of receiving self-initiated polygenic risk scores from a third-party website. Eur J Hum Genet. 2023;31:424–9.

    PubMed  Google Scholar 

  63. Peck L, Borle K, Folkersen L, Austin J. Why do people seek out polygenic risk scores for complex disorders, and how do they understand and react to results? Eur J Hum Genet. 2022;30:81–7.

    PubMed  Google Scholar 

  64. Bunnik EM, Schermer MH, JW Janssens AC. The role of disease characteristics in the ethical debate on personal genome testing. BMC Med Genomics. 2012;5:4.

    PubMed  PubMed Central  Google Scholar 

  65. Garrison NA, Brothers KB, Goldenberg AJ, Lynch JA. Genomic contextualism: shifting the rhetoric of genetic exceptionalism. Am J Bioeth AJOB. 2019;19:51–63.

    PubMed  Google Scholar 

Download references

Acknowledgements

We thank the CAN.HEAL consortium (EU4H-2021-PJ2). Discussions with its members have inspired and contributed to the development of the present work.

Funding

This work has received funding from the European Union Horizon 2020 research and innovation program: “Precision Medicine at the interface of Translational Research and Systems Medicine (TranSYS)” (H2020-MSCA-ITN-2019).

Author information

Authors and Affiliations

  1. Department of Public Health and Primary Care, Centre for Biomedical Ethics and Law, KU Leuven, Leuven, Belgium

    Lara Andreoli & Kris Dierickx

  2. Department of Human Genetics, KU Leuven, Leuven, Belgium

    Hilde Peeters & Kristel Van Steen

Authors
  1. Lara Andreoli
    View author publications

    Search author on:PubMed Google Scholar

  2. Hilde Peeters
    View author publications

    Search author on:PubMed Google Scholar

  3. Kristel Van Steen
    View author publications

    Search author on:PubMed Google Scholar

  4. Kris Dierickx
    View author publications

    Search author on:PubMed Google Scholar

Contributions

LA: Conceptualization; methodology; data analysis; data curation; writing—original draft; review and editing. HP: Conceptualization; data analysis; writing—review and editing. KVS: Conceptualization; data analysis; writing—review and editing. Kris Dierickx: Conceptualization; methodology; data analysis; writing—review and editing.

Corresponding author

Correspondence to Lara Andreoli.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Andreoli, L., Peeters, H., Van Steen, K. et al. Polygenic risk scores in the clinic: a systematic review of stakeholders’ perspectives, attitudes, and experiences. Eur J Hum Genet 33, 266–280 (2025). https://doi.org/10.1038/s41431-024-01747-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41431-024-01747-z

This article is cited by

Search

Advanced search

Quick links