Polygenic risk scores cannot make their mark on psychiatry without considering epigenetics

Area of Science:

• Genetics
• Developmental Psychology
• Psychiatry

Background:

• The utility of polygenic risk scores (PRS) in understanding complex traits like development and mental illness is under active investigation.
• Existing research often focuses on genetic heritability without fully incorporating environmental influences on gene expression.

Purpose of the Study:

• To critically evaluate the limitations of polygenic risk scores (PRS) in the context of developmental and mental illness research.
• To highlight the importance of considering epigenetic mechanisms in genetic studies.
• To discuss the potential risks and drawbacks of over-reliance on PRS.

Main Methods:

• This is a commentary, not an empirical study.
• It involves a critical review of existing literature and theoretical arguments.
• The authors expand upon the implications of epigenetic mechanisms for PRS utility.

Main Results:

• The study identifies a significant omission in current discussions of PRS: the role of epigenetics.
• Epigenetic mechanisms, which involve environmental influences on gene function, can limit the predictive power of PRS.
• Over-reliance on PRS may overlook crucial developmental and environmental factors in mental illness.

Conclusions:

• Epigenetics presents a fundamental challenge to the universal applicability of PRS in studying development and mental illness.
• Future research must integrate epigenetic factors to improve the accuracy and relevance of genetic risk prediction.
• A nuanced approach is necessary, acknowledging the limitations of PRS and the complex interplay of genes and environment.