Polygenic risk scores PRS

PRS will force a reckoning with pre-existing questions concerning biomarkers, namely the relevance of self-reported race, ethnicity and ancestry, and the relationship of risk factors to disease diagnoses. In this Opinion, we argue that despite the parallels to the monogenic setting, new work is urgently needed to gather data, consider normative implications, and develop best practices around this emerging branch of genomics.

https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00829-7

"PRS suffer from an interpretation problem: we are not yet sure what conclusions can be drawn from them. While some of the predictive signal captured in PRS comes from direct genetic effects, i.e., from variants that influence the phenotype of the individual, other predictive signals are also captured in a standard non-family-based GWAS. These include indirect genetic effects, for example genetic nurture url=https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00829-7#ref-CR17]17[/url. Effects of assortative mating and environmental confounding are also captured. In addition to these forms of gene-environment correlation, gene-by-environment interactions, where the same variant has a different overall effect in different environments, may also play a role. It is therefore not appropriate to straightforwardly draw causal conclusions from PRS"
Lewis, A.C.F., Green, R.C. Polygenic risk scores in the clinic: new perspectives needed on familiar ethical issues. Genome Med 13, 14 (2021). https://doi.org/10.1186/s13073-021-00829-7