bioinfo-statistics
Heritable polygenic editing에 대한 empirical modeling 논문 본문
https://www.nature.com/articles/s41588-025-02105-5
Fletcher, M. A model of heritable genome editing for complex traits. Nat Genet 57, 280 (2025). https://doi.org/10.1038/s41588-025-02105-5
Genome-wide association studies have identified thousands of trait-associated loci, but translating these findings into improved health outcomes is non-trivial. With the advent of CRISPR and related methods, there is increasing interest in applying gene editing in humans for this aim — most prominently the example of He Jiankui — although doing so in the germline and therefore generating heritable variation remains highly controversial. Visscher et al. present an empirical model of the potential population-level health impacts of editing up to 10 polygenic (that is, common) variants, suggesting that this could reduce common disease lifetime prevalence (for example, from 10% to 0.2% for type 2 diabetes).
https://www.nature.com/articles/s41586-024-08300-4
Visscher, P.M., Gyngell, C., Yengo, L. et al. Heritable polygenic editing: the next frontier in genomic medicine?. Nature 637, 637–645 (2025). https://doi.org/10.1038/s41586-024-08300-4
Abstract
Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. ... attempt to predict the consequences of altering specific variants associated with polygenic diseases. ... 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.
...ethical issues.... deepen health inequalities. Further, ...can increase the risk of some diseases while decreasing that of others, .... ethical challenges related to pleiotropy and genetic diversity.
