Pathway polygenic risk scores (pPRS) for the analysis of gene-environment interaction.

ABSTRACT: A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e. interacts with, important environmental (E) risk factors. Detection of a PRS by environment (PRS x E) interaction may provide clues to underlying biology and can be useful in developing targeted prevention strategies for modifiable risk factors. The standard PRS may include a subset of variants that interact with E but a much larger subset of variants that affect disease without regard to E. This latter subset will dilute the underlying signal in former subset, leading to reduced power to detect PRS x E interaction. We explore the use of pathway-defined PRS (pPRS) scores, using state of the art tools to

SUBMITTER: Gauderman WJ 

PROVIDER: S-EPMC12352875 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature