Heritable polygenic editing: the next frontier in genomic medicine?

Area of Science:

• Genetics
• Bioethics
• Medical Ethics

Background:

• Germline genome editing, including polygenic applications, is anticipated to be feasible within 30 years.
• Existing literature discusses ethical concerns and potential benefits of germline genome editing.
• No prior studies have predicted the consequences of altering variants for polygenic diseases.

Purpose of the Study:

• To analyze the potential impact of polygenic genome editing on disease susceptibility.
• To explore the ethical implications of heritable polygenic editing (HPE).
• To model the societal effects of HPE, focusing on health inequalities and genetic diversity.

Main Methods:

• Theoretical modeling of polygenic genome editing.
• Calculations to assess disease risk reduction and changes in risk factors.
• Ethical analysis of HPE considering pleiotropy and genetic diversity.

Main Results:

• Polygenic genome editing could drastically reduce susceptibility to complex diseases like heart disease, Alzheimer's, and schizophrenia.
• Significant alterations in risk factors (e.g., LDL cholesterol, blood pressure) are theoretically achievable.
• HPE may exacerbate health inequalities and presents challenges related to pleiotropy and genetic diversity.

Conclusions:

• Polygenic genome editing offers potential for extreme disease risk reduction but poses significant ethical challenges.
• The ethical considerations of HPE necessitate a collectivist perspective, evaluating impacts on individuals, families, and society.
• Addressing the complexities of HPE requires careful consideration of its effects on health equity and the human gene pool.