Polygenic embryo screening: quo vadis?
Ethics
PGT-P
Points to consider
Polygenic embryo screening
Polygenic risk scores
Preimplantation genetic testing
Journal
Journal of assisted reproduction and genetics
ISSN: 1573-7330
Titre abrégé: J Assist Reprod Genet
Pays: Netherlands
ID NLM: 9206495
Informations de publication
Date de publication:
15 Jun 2024
15 Jun 2024
Historique:
received:
05
04
2024
accepted:
06
06
2024
medline:
16
6
2024
pubmed:
16
6
2024
entrez:
15
6
2024
Statut:
aheadofprint
Résumé
Recently, the use of polygenic risk scores in embryo screening (PGT-P) has been introduced on the premise of reducing polygenic disease risk through embryo selection. However, it has been met with extensive critique: considered "technology-driven" rather than "evidence-based", concerns exist about its validity, utility, ethics, and societal effects. Its scientific foundations and criticisms thus need to be carefully considered. However, seeing as PGT-P is already offered in some settings, further questions need to be addressed, in order to give due diligence to various aspects of PGT-P. By examining the complexities of clinical introduction of PGT-P, we discuss whether PGT-P could be responsibly implemented in the first place, what elements need to be addressed if PGT-P is clinically implemented, and subsequently how counselling and decision-making of its users could be envisaged. By dissecting these elements, we provide an overview of important practical questions of PGT-P and emphasize elements of PGT-P that we think have yet to be given sufficient attention. These questions and elements are for example related to the potential target group, scope, and decision-making possibilities of PGT-P. The aspects we raise are crucial to consider by the scientific community and policy makers for the development of guidelines and/or an ethical framework for PGT-P.
Identifiants
pubmed: 38879662
doi: 10.1007/s10815-024-03169-8
pii: 10.1007/s10815-024-03169-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Horizon 2020
ID : 813707
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
De Rycke M, Berckmoes V, De Vos A, Van De Voorde S, Verdyck P, Verpoest W, et al. Clinical experience of preimplantation genetic testing. Reproduction. 2020;160:A45–58.
pubmed: 33112789
doi: 10.1530/REP-20-0082
Sciorio R, Dattilo M. PGT-A preimplantation genetic testing for aneuploidies and embryo selection in routine ART cycles: time to step back? Clin Genet. 2020;98(2):107–15.
pubmed: 32141057
doi: 10.1111/cge.13732
Treff NR, Eccles J, Lello L, Bechor E, Hsu J, Plunkett K, et al. Utility and first clinical application of screening embryos for polygenic disease risk reduction. Front Endocrinol (Lausanne). 2019;10:845.
pubmed: 31920964
doi: 10.3389/fendo.2019.00845
Kumar A, Im K, Banjevic M, Ng PC, Tunstall T, Garcia G, et al. Whole-genome risk prediction of common diseases in human preimplantation embryos. Nat Med. 2022;28(3):513–6.
pubmed: 35314819
pmcid: 8938270
doi: 10.1038/s41591-022-01735-0
Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018;19(9):581–90.
pubmed: 29789686
doi: 10.1038/s41576-018-0018-x
Lewis CM, Vassos E. Polygenic risk scores: from research tools to clinical instruments. Genome Med. 2020;12(1):44.
pubmed: 32423490
pmcid: 7236300
doi: 10.1186/s13073-020-00742-5
Polygenic Risk Score Task Force of the International Common Disease A. Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps. Nat Med. 2021;27(11):1876–84.
doi: 10.1038/s41591-021-01549-6
ESHRE PGT-M Working Group, Carvalho F, Moutou C, Dimitriadou E, Dreesen J, Gimenez C, et al. ESHRE PGT Consortium good practice recommendations for the detection of monogenic disorders. Hum Reprod Open. 2020;2020(3):hoaa018.
pmcid: 7257022
doi: 10.1093/hropen/hoaa018
ESHRE PGT-SR/PGT-A Working Group, Coonen E, Rubio C, Christopikou D, Dimitriadou E, Gontar J, et al. ESHRE PGT Consortium good practice recommendations for the detection of structural and numerical chromosomal aberrations. Hum Reprod Open. 2020;2020(3):hoaa017.
pmcid: 7257111
doi: 10.1093/hropen/hoaa017
ESHRE Working Group on Chromosomal Mosaicism, De Rycke M, Capalbo A, Coonen E, Coticchio G, Fiorentino F, et al. ESHRE survey results and good practice recommendations on managing chromosomal mosaicism. Hum Reprod Open. 2022;2022(4):hoac044.
pmcid: 9637425
doi: 10.1093/hropen/hoac044
Leigh D, Cram DS, Rechitsky S, Handyside A, Wells D, Munne S, et al. PGDIS position statement on the transfer of mosaic embryos 2021. Reprod Biomed Online. 2022;45(1):19–25.
pubmed: 35523707
doi: 10.1016/j.rbmo.2022.03.013
Practice Committee and Genetic Counseling Professional Group (GCPG) of the American Society for Reproductive Medicine. Clinical management of mosaic results from preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion. Fertil Steril. 2020;114(2):246–54.
doi: 10.1016/j.fertnstert.2020.05.014
Siermann M, Tsuiko O, Vermeesch JR, Raivio T, Borry P. A review of normative documents on preimplantation genetic testing: recommendations for PGT-P. Genet Med. 2022;24(6):1165–75.
pubmed: 35341652
doi: 10.1016/j.gim.2022.03.001
Ginoza MEC, Isasi R. Regulating preimplantation genetic testing across the world: a comparison of international policy and ethical perspectives. Cold Spring Harbor Perspect Med. 2020;10(5):a036681.
doi: 10.1101/cshperspect.a036681
Forzano F, Antonova O, Clarke A, de Wert G, Hentze S, Jamshidi Y, et al. The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. Eur J Hum Genet. 2021;30:493–5.
pubmed: 34916614
pmcid: 9090769
doi: 10.1038/s41431-021-01000-x
European Society of Human Reproduction and Embryology. ESHRE supports the position of ESHG on embryo selection based on polygenic risk scores. 2022. Available from: https://www.eshre.eu/Europe/Position-statements/PRS .
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(5):100803.
pubmed: 36920474
doi: 10.1016/j.gim.2023.100803
Lázaro-Muñoz G, Pereira S, Carmi S, Lencz T. Screening embryos for polygenic conditions and traits: ethical considerations for an emerging technology. Genet Med. 2021;23(3):432–4.
pubmed: 33106616
doi: 10.1038/s41436-020-01019-3
Pagnaer T, Siermann M, Borry P, Tsuiko O. Polygenic risk scoring of human embryos: a qualitative study of media coverage. BMC Med Ethics. 2021;22(1):125.
pubmed: 34537037
pmcid: 8449454
doi: 10.1186/s12910-021-00694-4
Karavani E, Zuk O, Zeevi D, Barzilai N, Stefanis NC, Hatzimanolis A, et al. Screening human embryos for polygenic traits has limited utility. Cell. 2019;179(6):1424–35.
pubmed: 31761530
pmcid: 6957074
doi: 10.1016/j.cell.2019.10.033
Turley P, Meyer MN, Wang N, Cesarini D, Hammonds E, Martin AR, et al. Problems with using polygenic scores to select embryos. N Engl J Med. 2021;385(1):78–86.
pubmed: 34192436
pmcid: 8387884
doi: 10.1056/NEJMsr2105065
Lencz T, Backenroth D, Granot-Hershkovitz E, Green A, Gettler K, Cho JH, et al. Utility of polygenic embryo screening for disease depends on the selection strategy. eLife. 2021;10:e64716.
Polyakov A, Amor DJ, Savulescu J, Gyngell C, Georgiou EX, Ross V, et al. Polygenic risk score for embryo selection—not ready for prime time. Hum Reprod. 2022;37(10):2229–36.
pubmed: 35852518
pmcid: 9527452
doi: 10.1093/humrep/deac159
Siermann M, Valcke O, Vermeesch JR, Raivio T, Tšuiko O, Borry P. Limitations, concerns and potential: attitudes of healthcare professionals toward preimplantation genetic testing using polygenic risk scores. Eur J Hum Genet. 2023;31:1133–8.
pubmed: 36935419
doi: 10.1038/s41431-023-01333-9
Treff NR, Savulescu J, de Melo-Martín I, Shulman LP, Feinberg EC. Should preimplantation genetic testing for polygenic disease be offered to all – or none? Fertil Steril. 2022;117(6):1162–7.
pubmed: 35513906
doi: 10.1016/j.fertnstert.2022.03.017
Johnston J, Matthews LJ. Polygenic embryo testing: understated ethics, unclear utility. Nat Med. 2022;28:446–8.
pubmed: 35314818
pmcid: 9208380
doi: 10.1038/s41591-022-01743-0
Koslov M. The controversial embryo tests that promise a better baby. Nature. 2022;609:668–71.
doi: 10.1038/d41586-022-02961-9
Griffin DK, Gordon AT. Preimplantation testing for polygenic disease (PGT-P): brave new world or mad pursuit? DNA. 2023;3(2):104–8.
doi: 10.3390/dna3020008
Siermann M, Valcke O, Vermeesch JR, Raivio T, Tšuiko O, Borry P. “Are we not going too far?”: socio-ethical considerations of preimplantation genetic testing using polygenic risk scores according to healthcare professionals. Soc Sci Med. 2024;343:1–8.
doi: 10.1016/j.socscimed.2024.116599
Orchid. Have healthy babies. 2024. Available from: https://www.orchidhealth.com/ . Accessed 7 Feb 2024.
LifeView (powered by Genomic Prediction). Better tests. Better Outcomes. 2024. Available from: https://lifeview.com/ . Accessed 7 Feb 2024.
Meyer MN, Tan T, Benjamin DJ, Laibson D, Turley P. Public views on polygenic screening of embryos. Science. 2023;379(6632):541–3.
pubmed: 36758092
pmcid: 9999424
doi: 10.1126/science.ade1083
Zhang S, Johnson RA, Novembre J, Freeland E, Conley D. Public attitudes toward genetic risk scoring in medicine and beyond. Soc Sci Med. 2021;274:113796.
pubmed: 33684700
doi: 10.1016/j.socscimed.2021.113796
Furrer RA, Barlevy D, Pereira S, Carmi S, Lencz T, Lazaro-Munoz G. Public attitudes, interests, and concerns regarding polygenic embryo screening. JAMA Netw Open. 2024;7(5):e2410832.
pubmed: 38743425
pmcid: 11094562
doi: 10.1001/jamanetworkopen.2024.10832
Treff NR, Zimmerman R, Bechor E, Hsu J, Rana B, Jensen J, et al. Validation of concurrent preimplantation genetic testing for polygenic and monogenic disorders, structural rearrangements, and whole and segmental chromosome aneuploidy with a single universal platform. Eur J Med Genet. 2019;62(8):103647.
pubmed: 31026593
doi: 10.1016/j.ejmg.2019.04.004
Treff NR, Eccles J, Marin D, Messick E, Lello L, Gerber J, et al. Preimplantation genetic testing for polygenic disease relative risk reduction: evaluation of genomic index performance in 11,883 adult sibling pairs. Genes (Basel). 2020;11(6):648.
pubmed: 32545548
pmcid: 7349610
doi: 10.3390/genes11060648
Lello L, Raben TG, Hsu SDH. Sibling validation of polygenic risk scores and complex trait prediction. Sci Rep. 2020;10(1):13190.
pubmed: 32764582
pmcid: 7411027
doi: 10.1038/s41598-020-69927-7
Lello L, Tellier LCAM. Polygenic risk scores, PGT-P, and IVF: sibling and non-European ancestry validations. Fertil Steril. 2021;116(3, Supplement):e20.
Lello L, Hsu M, Widen E, Raben TG. Sibling variation in polygenic traits and DNA recombination mapping with UK Biobank and IVF family data. Sci Rep. 2023;13(1):376.
pubmed: 36611071
pmcid: 9825593
doi: 10.1038/s41598-023-27561-z
Widen E, Lello L, Raben TG, Tellier L, Hsu SDH. Polygenic health index, general health, and pleiotropy: sibling analysis and disease risk reduction. Sci Rep. 2022;12(1):18173.
pubmed: 36307513
pmcid: 9616929
doi: 10.1038/s41598-022-22637-8
Lu T, Zhou S, Wu H, Forgetta V, Greenwood CMT, Richards JB. Individuals with common diseases but with a low polygenic risk score could be prioritized for rare variant screening. Genet Med. 2021;23(3):508–15.
pubmed: 33110269
doi: 10.1038/s41436-020-01007-7
Lu T, Forgetta V, Richards JB, Greenwood CMT. Polygenic risk score as a possible tool for identifying familial monogenic causes of complex diseases. Genet Med. 2022;24(7):1545–55.
pubmed: 35460399
doi: 10.1016/j.gim.2022.03.022
Zhang H, Zhan J, Jin J, Zhang J, Lu W, Zhao R, et al. A new method for multiancestry polygenic prediction improves performance across diverse populations. Nat Genet. 2023;55(10):1757–68.
pubmed: 37749244
pmcid: 10923245
doi: 10.1038/s41588-023-01501-z
Goldberg C. Picking embryos with best health odds sparks New DNA debate. 2021. Available from: https://www.bloomberg.com/news/articles/2021-09-17/picking-embryos-with-best-health-odds-sparks-new-dna-debate#xj4y7vzkg .
Barlevy D, Cenolli I, Campbell T, Furrer R, Mukherjee M, Kostick-Quenet KM, et al. Patient interest in and clinician reservations on polygenic embryo screening: a qualitative study of stakeholder perspectives. J Assist Reprod Genet. 2024;41(5):1221–31.
pubmed: 38470550
doi: 10.1007/s10815-024-03074-0
Siermann M, Claesen Z, Pasquier L, Raivio T, Tšuiko O, Vermeesch JR, et al. A systematic review of the views of healthcare professionals on the scope of preimplantation genetic testing. J Community Genet. 2022;13:1–11.
pubmed: 35028914
pmcid: 8799829
doi: 10.1007/s12687-021-00573-w
Lemke T, Rüppel J. Social dimensions of preimplantation genetic diagnosis: a literature review. New Genet Soc. 2018;38(1):80–112.
doi: 10.1080/14636778.2018.1549983
Boardman FK, Clark CC. What is a ‘serious’ genetic condition? The perceptions of people living with genetic conditions. Eur J Hum Genet. 2022;30:160–9.
pubmed: 34565797
doi: 10.1038/s41431-021-00962-2
Siermann M, Van der Schoot V, Bunnik EM, Borry P. Ready for polygenic risk scores? An analysis of regulation of preimplantation genetic testing in European countries. Hum Reprod. 2024;39(5):1117–30.
pubmed: 38514452
doi: 10.1093/humrep/deae049
Lewis ACF, Green RC. Polygenic risk scores in the clinic: new perspectives needed on familiar ethical issues. Genome Med. 2021;13(1):14.
pubmed: 33509269
pmcid: 7844961
doi: 10.1186/s13073-021-00829-7
Lencz T, Sabatello M, Docherty A, Peterson RE, Soda T, Austin J, et al. Concerns about the use of polygenic embryoscreening for psychiatric and cognitive traits. Lancet Psychiatry. 2022;9(10):P838–44.
doi: 10.1016/S2215-0366(22)00157-2
Pereira S, Carmi S, Altarescu G, Austin J, Barlevy D, Hershlag A, et al. Polygenic embryo screening: four clinical considerations warrant further attention. Hum Reprod. 2022;37(7):1375–8.
pubmed: 35604365
pmcid: 9247413
doi: 10.1093/humrep/deac110
Graham ME, Jelin A, Hoon AH Jr, Wilms Floet AM, Levey E, Graham EM. Assisted reproductive technology: short- and long-term outcomes. Dev Med Child Neurol. 2023;65(1):38–49.
pubmed: 35851656
doi: 10.1111/dmcn.15332
Hughes T, Bracewell-Milnes T, Saso S, Jones BP, Almeida PA, Maclaren K, et al. A review on the motivations, decision-making factors, attitudes and experiences of couples using pre-implantation genetic testing for inherited conditions. Human Reproduction Update. 2021;27(5):944–66.
pubmed: 33969393
doi: 10.1093/humupd/dmab013
Malina A, Blaszkiewicz A, Owczarz U. Psychosocial aspects of infertility and its treatment. Ginekol Pol. 2016;87(7):527–31.
pubmed: 27504947
doi: 10.5603/GP.2016.0038
Eccles J, Marin D, Duffy L, Chen SH, Treff NR. Rate of patients electing for polygenic risk scores in preimplantation genetic testing. Fertil Steril. 2021;116(3):e267–8.
doi: 10.1016/j.fertnstert.2021.07.717
Human Fertilisation & Embryology Authority. Code of practice 9.0 (revised December 2019). 2019.
De Wert G, Dondorp W, Shenfield F, Devroey P, Tarlatzis B, Barri P, et al. ESHRE task force on ethics and law22: preimplantation genetic diagnosis. Hum Reprod. 2014;29(8):1610–7.
pubmed: 24927929
doi: 10.1093/humrep/deu132
Chen SC, Wasserman DT. A framework for unrestricted prenatal whole-genome sequencing: respecting and enhancing the autonomy of prospective parents. Am J Bioeth. 2017;17(1):3–18.
pubmed: 27996923
doi: 10.1080/15265161.2016.1251632
Laberge A-M, Burke W. Avoiding the technological imperative: criteria for genetic screening programs. OBM Genet. 2017;01(03):1.
doi: 10.21926/obm.genet.1703006
Hens K, Dondorp WJ, Geraedts JP, de Wert GM. Comprehensive embryo testing. Experts’ opinions regarding future directions: an expert panel study on comprehensive embryo testing. Human Reproduction. 2013;28(5):1418–25.
pubmed: 23416277
doi: 10.1093/humrep/det018
Ray F. Embryo selection from polygenic risk scores enters market as clinical value remains unproven. 2021. Available from: https://www.genomeweb.com/sequencing/embryo-selection-polygenic-risk-scores-enters-market-clinical-value-remains-unproven#.YdVrVmjMJPZ .
Michailidou K, Lindstrom S, Dennis J, Beesley J, Hui S, Kar S, et al. Association analysis identifies 65 new breast cancer risk loci. Nature. 2017;551(7678):92–4.
pubmed: 29059683
pmcid: 5798588
doi: 10.1038/nature24284
Trinder M, Francis GA, Brunham LR. Association of monogenic vs polygenic hypercholesterolemia with risk of atherosclerotic cardiovascular disease. JAMA Cardiol. 2020;5(4):390–9.
pubmed: 32049305
pmcid: 7042820
doi: 10.1001/jamacardio.2019.5954
Siermann M, Vermeesch JR, Raivio T, Vanhie A, Peeraer K, Tšuiko O, et al. Perspectives of preimplantation genetic testing patients in Belgium on the ethics of polygenic embryo screening. Reproductive Biomedicine Online. 2024.
Lambert SA, Abraham G, Inouye M. Towards clinical utility of polygenic risk scores. Hum Mol Genet. 2019;28(R2):R133–42.
pubmed: 31363735
doi: 10.1093/hmg/ddz187
Fahed AC, Wang M, Homburger JR, Patel AP, Bick AG, Neben CL, et al. Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions. Nat Commun. 2020;11(1):3635.
pubmed: 32820175
pmcid: 7441381
doi: 10.1038/s41467-020-17374-3
Kuchenbaecker KB, McGuffog L, Barrowdale D, Lee A, Soucy P, Dennis J, et al. Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2017;109(7):djw302.
Mars N, Widen E, Kerminen S, Meretoja T, Pirinen M, Della Briotta Parolo P, et al. The role of polygenic risk and susceptibility genes in breast cancer over the course of life. Nat Commun. 2020;11(1):6383.
pubmed: 33318493
pmcid: 7736877
doi: 10.1038/s41467-020-19966-5
Mertes H, Pennings G. Bioethics in human reproduction (human reproductive genetics). In: García-Velasco JA, Seli E, editors. Human reproductive genetics: emerging technologies and clinical applications. Cambridge (MA): Academic Press; 2020. p. 283–93.
doi: 10.1016/B978-0-12-816561-4.00018-1
Vukovic P, Peccatori FA, Massarotti C, Miralles MS, Beketic-Oreskovic L, Lambertini M. Preimplantation genetic testing for carriers of BRCA1/2 pathogenic variants. Crit Rev Oncol Hematol. 2021;157:103201.
pubmed: 33333149
doi: 10.1016/j.critrevonc.2020.103201
Spinella F, Bronet F, Carvalho F, Coonen E, De Rycke M, Rubio C, et al. ESHRE PGT Consortium data collection XXI: PGT analyses in 2018. Hum Reprod Open. 2023;2023(2):hoad010.
pubmed: 37091225
pmcid: 10121336
doi: 10.1093/hropen/hoad010
van der Schoot V, Dondorp W, Dreesen J, Coonen E, Paulussen ADC, de Wert G, et al. Preimplantation genetic testing for more than one genetic condition: clinical and ethical considerations and dilemmas. Hum Reprod. 2019;34(6):1146–54.
pubmed: 31119284
doi: 10.1093/humrep/dez059
Mortimer R, Ginsburg E. Preimplantation genetic testing for aneuploidy: has the controversy settled? A Review. Curr Obstet Gynecol Rep. 2022;11(1):48–54.
doi: 10.1007/s13669-021-00322-3
van Loendersloot L, van Wely M, van der Veen F, Bossuyt P, Repping S. Selection of embryos for transfer in IVF: ranking embryos based on their implantation potential using morphological scoring. Reprod Biomed Online. 2014;29(2):222–30.
pubmed: 24925309
doi: 10.1016/j.rbmo.2014.04.016
Mastenbroek S, De Wert G, Adashi EY. The imperative of responsible innovation in reproductive medicine. N Engl J Med. 2021;385(22):2096–100.
pubmed: 34818487
doi: 10.1056/NEJMsb2101718
Belgisch Staatsblad. Wet betreffende de medisch begeleide voortplanting en de bestemming van de overtallige embryo’s en de gameten, bl. 38575. 2007.
Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219–24.
pubmed: 30104762
pmcid: 6128408
doi: 10.1038/s41588-018-0183-z
Cheng L, Meiser B, Kirk E, Kennedy D, Barlow-Stewart K, Kaur R. Decisional needs of patients considering preimplantation genetic testing: a systematic review. Reprod Biomed Online. 2022;44(5):839–52.
pubmed: 35183447
doi: 10.1016/j.rbmo.2021.12.011
Zeiler K. Reproductive autonomous choice – a cherished illusion? Reproductive autonomy examined in the context of preimplantation genetic diagnosis. Med Health Care Philos. 2004;7:175–83.
pubmed: 15379192
doi: 10.1023/B:MHEP.0000034323.68025.d5
Hens K, Dondorp W, Handyside AH, Harper J, Newson AJ, Pennings G, et al. Dynamics and ethics of comprehensive preimplantation genetic testing: a review of the challenges. Hum Reprod Update. 2013;19(4):366–75.
pubmed: 23466750
doi: 10.1093/humupd/dmt009
Tellier LCAM, Eccles J, Treff NR, Lello L, Fishel S, Hsu S. Embryo screening for polygenic disease risk: recent advances and ethical considerations. Genes (Basel). 2021;12(8):1105.
pubmed: 34440279
pmcid: 8393569
doi: 10.3390/genes12081105
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(1):114.
pubmed: 36207733
pmcid: 9540716
doi: 10.1186/s13073-022-01117-8
Borry P, Evers-Kiebooms G, Cornel MC, Clarke A, Dierickx K, Public, et al. Genetic testing in asymptomatic minors: background considerations towards ESHG Recommendations. European J Hum Genet. 2009;17(6):711–19.
Menzel MB, Madrigal VN. Genetic testing and screening of children. In: Nortjé N, Bester JC, editors. Pediatric ethics: theory and practice. Switzerland: Springer; 2021. p. 313–28.