https://www.nature.com/articles/s41593-023-01333-4 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. Advertisement Advertisement Nature Neuroscience * View all journals * Search * Log in * Explore content * About the journal * Publish with us * Subscribe * Sign up for alerts * RSS feed 1. nature 2. nature neuroscience 3. perspectives 4. article * Perspective * Published: 22 May 2023 Addressing the ethical and societal challenges posed by genome-wide association studies of behavioral and brain-related traits * Matthieu C. de Hemptinne^1 & * Danielle Posthuma ORCID: orcid.org/0000-0001-7582-2365^1 Nature Neuroscience (2023)Cite this article * 3 Altmetric * Metrics details Subjects * Databases * Genome-wide association studies Abstract Genome-wide association studies have led to the identification of robust statistical associations of genetic variants with numerous brain-related traits, including neurological and psychiatric conditions, and psychological and behavioral measures. These results may provide insight into the biology underlying these traits and may facilitate clinically useful predictions. However, these results also carry the risk of harm, including possible negative effects of inaccurate predictions, violations of privacy, stigma and genomic discrimination, raising serious ethical and legal implications. Here, we discuss ethical concerns surrounding the results of genome-wide association studies for individuals, society and researchers. Given the success of genome-wide association studies and the increasing availability of nonclinical genomic prediction technologies, better laws and guidelines are urgently needed to regulate the storage, processing and responsible use of genetic data. Also, researchers should be aware of possible misuse of their results, and we provide guidance to help avoid such negative impacts on individuals and society. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution Access options Access through your institution Access through your institution Change institution Buy or subscribe Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 per month cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $189.00 per year only $15.75 per issue Learn more Rent or buy this article Get just this article for as long as you need it $39.95 Learn more Prices may be subject to local taxes which are calculated during checkout Additional access options: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support Fig. 1: Embryo selection for desirable traits may come with some unexpected consequences. [41593_2023_1333_Fig1_HTML] Fig. 2: Genetic exceptionalism and the impossibility to completely anonymize genetic data. [41593_2023_1333_Fig2_HTML] References 1. Uffelmann, E. et al. Genome-wide association studies. Nat. Rev. Methods Primers. 1, 59 (2021). Article CAS Google Scholar 2. Yengo, L. et al. A saturated map of common genetic variants associated with human height from 5.4 million individuals of diverse ancestries. Nature 610, 704-712 (2022). 3. Jansen, P. R. et al. Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence. Nat. Commun. 11, 5606 (2020). Article CAS PubMed PubMed Central Google Scholar 4. Klein, R. J. et al. Complement factor H polymorphism in age-related macular degeneration. Science 308, 385-389 (2005). Article CAS PubMed Central Google Scholar 5. Choi, S. W., Mak, T. S. H. & O'Reilly, P. F. A guide to performing Polygenic Risk Score analyses. Nat. Protoc. 15, 2759-2772 (2020). 6. Khera, A. V. et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat. Genet. 50, 1219-1224 (2018). Article CAS PubMed PubMed Central Google Scholar 7. Landi, I. et al. Prognostic value of polygenic risk scores for adults with psychosis. Nat. Med. 27, 1576-1581 (2021). Article CAS PubMed PubMed Central Google Scholar 8. Adeyemo, A. et al. Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps. Nat. Med. 27, 1876-1884 (2021). This is a comprehensive summary of the state of polygenic score research, and includes thoughtful discussion on the needs and challenges as PRSs move closer to widespread use in the clinic. Article Google Scholar 9. Rossello, X. et al. Risk prediction tools in cardiovascular disease prevention: a report from the ESC Prevention of CVD Programme led by the European Association of Preventive Cardiology (EAPC) in collaboration with the Acute Cardiovascular Care Association (ACCA) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP). Eur. Heart J. Acute Cardiovasc. Care 9, 522-532 (2020). Article Google Scholar 10. European Commission. Joint Research Centre. Genome-wide association studies, polygenic scores and social science genetics: overview and policy implications (Publications Office, 2019). 11. Wray, N. R., Yang, J., Goddard, M. E. & Visscher, P. M. The genetic interpretation of area under the ROC curve in genomic profiling. PLoS Genet. 6, e1000864 (2010). Article PubMed PubMed Central Google Scholar 12. Chatterjee, N., Shi, J. & Garcia-Closas, M. Developing and evaluating polygenic risk prediction models for stratified disease prevention. Nat. Rev. Genet. 17, 392-406 (2016). Article CAS PubMed PubMed Central Google Scholar 13. Trubetskoy, V. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604, 502-508 (2022). Article CAS PubMed PubMed Central Google Scholar 14. Savage, J. E. et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat. Genet. 50, 912-919 (2018). Article CAS PubMed PubMed Central Google Scholar 15. Martin, A. R. et al. Current clinical use of polygenic scores will risk exacerbating health disparities. Nat. Genet. 51, 584-591 (2019). Article CAS PubMed PubMed Central Google Scholar 16. Mostafavi, H. et al. Variable prediction accuracy of polygenic scores within an ancestry group. eLife 9, e48376 (2020). Article CAS PubMed PubMed Central Google Scholar 17. Kong, A. et al. The nature of nurture: effects of parental genotypes. Science 359, 424-428 (2018). Article CAS PubMed Google Scholar 18. Office for Civil Rights: Health Information Privacy (US HHS, accessed 1 April 2023); https://www.hhs.gov/hipaa/index.html 19. Phillips, A. M. Reading the fine print when buying your genetic self online: direct-to-consumer genetic testing terms and conditions. New Genet. Soc. 36, 273-295 (2017). Article Google Scholar 20. 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. 30, 81-87 (2022). Article PubMed Google Scholar 21. Shoenbill, K., Fost, N., Tachinardi, U. & Mendonca, E. A. Genetic data and electronic health records: a discussion of ethical, logistical and technological considerations. J. Am. Med. Inform. Assoc. 21, 171-180 (2014). Article PubMed Google Scholar 22. Putt, S. et al. Exploration of experiences with and understanding of polygenic risk scores for bipolar disorder. J. Affect. Disord. 265, 342-350 (2020). Article CAS PubMed Google Scholar 23. Lewis, A. C. F. & Green, R. C. Polygenic risk scores in the clinic: new perspectives needed on familiar ethical issues. Genome Med. 13, 14 (2021). This paper provides a good overview of the different ethical issues related to the use of polygenic risk scores in clinical practice. Article PubMed PubMed Central Google Scholar 24. Green, R. C., Lautenbach, D. & McGuire, A. L. GINA, genetic discrimination, and genomic medicine. N. Engl. J. Med. 372, 397-399 (2015). Article CAS PubMed Google Scholar 25. Fost, N. Ethical issues in genetics. Pediatr. Clin. North Am. 39, 79-89 (1992). Article CAS PubMed Google Scholar 26. Joly, Y. et al. The Genetic Discrimination Observatory: confronting novel issues in genetic discrimination. Trends Genet. 37, 951-954 (2021). Article CAS PubMed Google Scholar 27. Tiller, J. et al. Genetic discrimination by Australian insurance companies: a survey of consumer experiences. Eur. J. Hum. Genet. 28, 108-113 (2020). Article PubMed Google Scholar 28. Clayton, E. W., Evans, B. J., Hazel, J. W. & Rothstein, M. A. The law of genetic privacy: applications, implications, and limitations. J. Law Biosci. 6, 1-36 (2019). Article PubMed PubMed Central Google Scholar 29. Phillips, A. et al. Informing relatives of their genetic risk: an examination of the Belgian legal context. Eur. J. Hum. Genet. https://doi.org/10.1038/s41431-021-01016-3 (2022). 30. Kraft, S. A., Duenas, D., Wilfond, B. S. & Goddard, K. A. B. The evolving landscape of expanded carrier screening: challenges and opportunities. Genet. Med. 21, 790-797 (2019). Article PubMed Google Scholar 31. Turley, P. et al. Problems with using polygenic scores to select embryos. N. Engl. J. Med. 385, 78-86 (2021). In this paper, the ethical and legal aspect of embryo selection using polygenic risk scores is discussed as well as the gains and the risks on society. Article PubMed PubMed Central Google Scholar 32. Kostick, K., Brannan, C., Pereira, S. & Lazaro-Munoz, G. Psychiatric genetics researchers' views on offering return of results to individual participants. Am. J. Med. Genet. B Neuropsychiatr. Genet. 180, 589-600 (2018). Article PubMed PubMed Central Google Scholar 33. Karavani, E. et al. Screening human embryos for polygenic traits has limited utility. Cell 179, 1424-1435 (2019). In this paper, theory, simulations and real data are used to assess the impact of embryo selection based on polygenic risk scores. It is shown that such predictions have wide confidence intervals and in practice are hardly useful. Article CAS PubMed PubMed Central Google Scholar 34. Ball, P. Polygenic screening of embryos is here, but is it ethical? (The Observer, 2021). 35. Baruch, S., Kaufman, D. & Hudson, K. L. Genetic testing of embryos: practices and perspectives of US in vitro fertilization clinics. Fertil. Steril. 89, 1053-1058 (2008). Article Google Scholar 36. Al-Khelaifi, F. et al. Genome-wide association study reveals a novel association between MYBPC3 gene polymorphism, endurance athlete status, aerobic capacity and steroid metabolism. Front. Genet. 11, 595 (2020). Article CAS PubMed Central Google Scholar 37. Morgan, M. D. et al. Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability. Nat. Commun. 9, 5271 (2018). Article PubMed Central Google Scholar 38. Dondorp, W. & de Wert, G. Refining the ethics of preimplantation genetic diagnosis: a plea for contextualized proportionality. Bioethics 33, 294-301 (2019). Article PubMed Google Scholar 39. Bayefsky, M. J. Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism. Reprod. Biomed. Soc. Online 3, 41-47 (2016). Article Google Scholar 40. Corveleyn, A., Morris, M., Zika, E., & Institute for Prospective Technological Studies. Preimplantation genetic diagnosis in Europe (Publications Office, 2007). 41. Bayefsky, M. Who should regulate preimplantation genetic diagnosis in the United States? AMA J. Ethics 20, 1160-1167 (2018). Article Google Scholar 42. Rodriguez, L. L., Brooks, L. D., Greenberg, J. H. & Green, E. D. The complexities of genomic identifiability. Science 339, 275-276 (2013). Article CAS PubMed Google Scholar 43. Homer, N. et al. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genet. 4, e1000167 (2008). Article PubMed PubMed Central Google Scholar 44. D. Conley. What's your polygenic score? Scientific American (13 March 2017). 45. Shabani, M. & Marelli, L. Re-identifiability of genomic data and the GDPR. EMBO Rep. 20, e48316 (2019). Article PubMed Central Google Scholar 46. Hansson, M. G. et al. The risk of re-identification versus the need to identify individuals in rare disease research. Eur. J. Hum. Genet. 24, 1553-1558 (2016). Article PubMed Central Google Scholar 47. Beil, A. et al. Disclosure of clinically actionable genetic variants to thoracic aortic dissection biobank participants. BMC Med. Genomics 14, 66 (2021). Article CAS PubMed PubMed Central Google Scholar 48. Wolf, S. M. Return of individual research results and incidental findings: facing the challenges of translational science. Annu. Rev. Genomics Hum. Genet. 14, 557-577 (2013). Article CAS PubMed PubMed Central Google Scholar 49. Wolf, S. M. The challenge of incidental findings. J. Law. Med. Ethics 36, 216-218 (2008). Article PubMed Central Google Scholar 50. De Clercq, E., Kaye, J., Wolf, S. M., Koenig, B. A. & Elger, B. S. Returning results in biobank research: global trends and solutions. Genet. Test. Mol. Biomark. 21, 128-131 (2017). Article Google Scholar 51. Bredenoord, A. L., Onland-Moret, N. C. & Van Delden, J. J. M. Feedback of individual genetic results to research participants: in favor of a qualified disclosure policy. Hum. Mutat. 32, 861-867 (2011). This article provides a very thoughtful overview of ethical issues concerning whether and when researchers have a moral obligation to return genetic research results to participants. It also includes clear suggestions on a qualified disclosure policy. Article PubMed Google Scholar 52. Jarvik, G. P. et al. Return of genomic results to research participants: the floor, the ceiling, and the choices in between. Am. J. Hum. Genet. 94, 818-826 (2014). Article CAS PubMed PubMed Central Google Scholar 53. Dashti, H. S. et al. Genome-wide association study of breakfast skipping links clock regulation with food timing. Am. J. Clin. Nutr. 110, 473-484 (2019). Article PubMed PubMed Central Google Scholar 54. van de Vegte, Y. J., Said, M. A., Rienstra, M., van der Harst, P. & Verweij, N. Genome-wide association studies and Mendelian randomization analyses for leisure sedentary behaviours. Nat. Commun. 11, 1770 (2020). Article PubMed PubMed Central Google Scholar 55. Coffee and Caffeine Genetics Consortium. et al. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol. Psychiatry 20, 647-656 (2015). Article Google Scholar 56. Gerard, R. W. The role of pure science. Science 88, 361-368 (1938). Article CAS PubMed Google Scholar 57. Carlson, J. & Harris, K. Quantifying and contextualizing the impact of bioRxiv preprints through automated social media audience segmentation. PLoS Biol. 18, e3000860 (2020). This paper introduces a method to assess the impact of preprints, which can aid in tracking online (mis)appropriation of GWAS results. Article CAS PubMed PubMed Central Google Scholar 58. Winkelman, W. D., Missmer, S. A., Myers, D. & Ginsburg, E. S. Public perspectives on the use of preimplantation genetic diagnosis. J. Assist. Reprod. Genet. 32, 665-675 (2015). Article PubMed PubMed Central Google Scholar 59. Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281-2308 (2013). Article CAS PubMed PubMed Central Google Scholar 60. Xu, M. CCR5-D32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool. Cell Biosci. 10, 48 (2020). Article PubMed PubMed Central Google Scholar 61. van Beers, B. C. Rewriting the human genome, rewriting human rights law? Human rights, human dignity, and human germline modification in the CRISPR era. J. Law Biosci. 7, lsaa006 (2020). Article PubMed PubMed Central Google Scholar 62. Coller, B. S. Ethics of human genome editing. Annu. Rev. Med. 70, 289-305 (2019). Article CAS PubMed Google Scholar 63. Read the Affordable Care Act, Health Care Law (HealthCare, accessed 1 April 2023); https://www.healthcare.gov/ where-can-i-read-the-affordable-care-act/1 64. EU Law - EUR-Lex (accessed 1 April 2023, EUR-Lex); https:// eur-lex.europa.eu/homepage.html?locale=en 65. Taylor, M. J., Wallace, S. E. & Prictor, M. United Kingdom: transfers of genomic data to third countries. Hum. Genet. 137, 637-645 (2018). Article CAS PubMed PubMed Central Google Scholar 66. Wertz, D. C. & Knoppers, B. M. Serious genetic disorders: can or should they be defined? Am. J. Med. Genet. 108, 29-35 (2002). Article PubMed Google Scholar 67. Botkin, J. R. Fetal privacy and confidentiality. Hastings Cent. Rep. 25, 32-39 (1995). Article CAS PubMed Google Scholar 68. Lazaro-Munoz, G., Pereira, S., Carmi, S. & Lencz, T. Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology. Genet. Med. 23, 432-434 (2021). This is a very clear commentary on ethical issues related to polygenic embryonic screening. Article PubMed Google Scholar 69. Ganna, A. et al. Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior. Science 365, eaat7693 (2019). Article CAS PubMed PubMed Central Google Scholar 70. Dawood, K., Bailey, J. M. & Martin, N. G. Genetic and Environmental Influences on Sexual Orientation. in Handbook of Behavior Genetics (ed. Kim, Y. K.) 11 (Springer, 2009). 71. Check Hayden, E. Ethics: taboo genetics. Nature 502, 26-28 (2013). Article CAS Google Scholar 72. Sniekers, S. et al. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nat. Genet. 49, 1107-1112 (2017). Article CAS PubMed PubMed Central Google Scholar 73. Hsu, S. Super-intelligent humans are coming. Nautilus (2 October 2014). 74. Bulik-Sullivan, B. K. et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291-295 (2015). Article CAS PubMed PubMed Central Google Scholar 75. Watanabe, K. et al. A global overview of pleiotropy and genetic architecture in complex traits. Nat. Genet. 51, 1339-1348 (2019). Article CAS Google Scholar 76. Verbanck, M., Chen, C.-Y., Neale, B. & Do, R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat. Genet. 50, 693-698 (2018). Article CAS PubMed PubMed Central Google Scholar 77. Brainstorm Consortium. et al. Analysis of shared heritability in common disorders of the brain. Science 360, eaap8757 (2018). Article Google Scholar 78. Hill, W. D., Harris, S. E. & Deary, I. J. What genome-wide association studies reveal about the association between intelligence and mental health. Curr. Opin. Psychol. 27, 25-30 (2019). Article PubMed Google Scholar 79. Lee, J. J. et al. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat. Genet. 50, 1112-1121 (2018). Article CAS PubMed Central Google Scholar 80. Lencz, T. et al. Concerns about the use of polygenic embryo screening for psychiatric and cognitive traits. Lancet Psychiatry https://doi.org/10.1016/S2215-0366(22)00157-2 (2022). Article PubMed PubMed Central Google Scholar 81. Wedow, R., Martschenko, D. O. & Trejo, S. Scientists must consider the risk of racist misappropriation of research (Scientific American, 2022). 82. Molteni, M. Buffalo shooting ignites a debate over the role of genetics researchers in white supremacist ideology. STAT (23 May 2022). 83. Wills, M. Are clusters races? A discussion of the rhetorical appropriation of Rosenberg et al.'s 'Genetic structure of human populations'. Philos. Theor. Pract. Biol. 9, 12 (2017). 84. Lewis, A. C. F. et al. Getting genetic ancestry right for science and society. Science 376, 250-252 (2022). Article CAS PubMed PubMed Central Google Scholar 85. Piffer, D. New genes, same results: group-level genotypic intelligence for 26 and 52 populations. topseudoscience (2 June 2017). 86. McKinley, J., Traub, A. & Closson, T. Gunman kills 10 at Buffalo supermarket in racist attack (The New York Times, 2022). 87. Jones, D. What is the 'great replacement' and how is it tied to the Buffalo shooting suspect? (NPR, 2022). Download references Acknowledgements This work is supported by the Netherlands Organization for Scientific Research--Gravitation project 'BRAINSCAPES: a Roadmap from Neurogenetics to Neurobiology' (024.004.012) and the European Research Council advanced grant 'From GWAS to Function' (ERC-2018-ADG 834057). We thank E. Uffelmann and P. Jansen for critical reading and fruitful discussions on earlier versions of this paper, and E. Bunnik for critically reading a pre-final version from a bioethical point of view. Author information Authors and Affiliations 1. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands Matthieu C. de Hemptinne & Danielle Posthuma Authors 1. Matthieu C. de Hemptinne View author publications You can also search for this author in PubMed Google Scholar 2. Danielle Posthuma View author publications You can also search for this author in PubMed Google Scholar Corresponding author Correspondence to Danielle Posthuma. Ethics declarations Competing interests The authors declare no competing interests. Peer review Peer review information Nature Neuroscience thanks Andrew McIntosh and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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 Verify currency and authenticity via CrossMark Cite this article de Hemptinne, M.C., Posthuma, D. Addressing the ethical and societal challenges posed by genome-wide association studies of behavioral and brain-related traits. Nat Neurosci (2023). https://doi.org/10.1038/ s41593-023-01333-4 Download citation * Received: 29 April 2022 * Accepted: 14 April 2023 * Published: 22 May 2023 * DOI: https://doi.org/10.1038/s41593-023-01333-4 Share this article Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative Access through your institution Buy or subscribe Access through your institution Change institution Buy or subscribe Advertisement Advertisement Explore content * Research articles * Reviews & Analysis * News & Comment * Videos * Current issue * Collections * Follow us on Twitter * Subscribe * Sign up for alerts * RSS feed About the journal * Aims & Scope * Journal Information * Journal Metrics * About the Editors * Our publishing models * Editorial Values Statement * Editorial Policies * Content Types * Web Feeds * Posters * Contact Publish with us * Submission Guidelines * For Reviewers * Language editing services * Submit manuscript Search Search articles by subject, keyword or author [ ] Show results from [All journals] Search Advanced search Quick links * Explore articles by subject * Find a job * Guide to authors * Editorial policies Nature Neuroscience (Nat Neurosci) ISSN 1546-1726 (online) ISSN 1097-6256 (print) nature.com sitemap About Nature Portfolio * About us * Press releases * Press office * Contact us Discover content * Journals A-Z * Articles by subject * Nano * Protocol Exchange * Nature Index Publishing policies * Nature portfolio policies * Open access Author & Researcher services * Reprints & permissions * Research data * Language editing * Scientific editing * Nature Masterclasses * Nature Research Academies * Research Solutions Libraries & institutions * Librarian service & tools * Librarian portal * Open research * Recommend to library Advertising & partnerships * Advertising * Partnerships & Services * Media kits * Branded content Career development * Nature Careers * Nature Conferences * Nature events Regional websites * Nature Africa * Nature China * Nature India * Nature Italy * Nature Japan * Nature Korea * Nature Middle East * Privacy Policy * Use of cookies * Manage cookies/Do not sell my data * Legal notice * Accessibility statement * Terms & Conditions * California Privacy Statement Springer Nature (c) 2023 Springer Nature Limited Close Nature Briefing Sign up for the Nature Briefing newsletter -- what matters in science, free to your inbox daily. Email address [ ] Sign up [ ] I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Close Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing * *