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Heritable polygenic editing: the next frontier in genomic medicine?

Abstract:

Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present1,2,3. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases. In this Analysis, we show that polygenic genome editing could theoretically yield extreme reductions in disease susceptibility. For example, editing a relatively small number of genomic variants could make a substantial difference to an individual’s risk of developing coronary artery disease, Alzheimer’s disease, major depressive disorder, diabetes and schizophrenia. Similarly, large changes in risk factors, such as low-density lipoprotein cholesterol and blood pressure, could, in theory, be achieved by polygenic editing. Although heritable polygenic editing (HPE) is still speculative, we completed calculations to discuss the underlying ethical issues. Our modelling demonstrates how the putatively positive consequences of gene editing at an individual level may deepen health inequalities. Further, as single or multiple gene variants can increase the risk of some diseases while decreasing that of others, HPE raises ethical challenges related to pleiotropy and genetic diversity. We conclude by arguing for a collectivist perspective on the ethical issues raised by HPE, which accounts for its effects on individuals, their families, communities and society4.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41586-024-08300-4

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Big Data Institute
Role:
Author
ORCID:
0000-0002-2143-8760
More by this author
Institution:
University of Oxford
Division:
HUMS
Department:
Philosophy Faculty
Oxford college:
St Cross College
Role:
Author
ORCID:
0000-0003-1691-6403


More from this funder
Funder identifier:
https://ror.org/029chgv08
Grant:
226801/Z/22/Z


Publisher:
Springer Nature
Journal:
Nature More from this journal
Volume:
637
Issue:
8046
Pages:
637-645
Publication date:
2025-01-08
Acceptance date:
2024-10-29
DOI:
EISSN:
1476-4687
ISSN:
0028-0836


Language:
English
Keywords:
Pubs id:
2078469
Local pid:
pubs:2078469
Deposit date:
2025-01-14

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