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 present1–3. 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. We discuss the potential consequences and ethical concerns of polygenic genome editing of human embryos to alter specific variants associated with polygenic diseases, highlighting the possibility of reducing disease susceptibility while exacerbating health inequalities.