Pathway Polygenic Risk Scores (pPRS) for the Analysis of Gene-environment Interaction

2024

Pathway Polygenic Risk Scores for Gene-Environment Interaction Analysis

Sample size: 78253 publication 10 minutes Evidence: high

Author Information

Author(s): Gauderman W. James, Fu Yubo, Queme Bryan, Kawaguchi Eric, Wang Yinqiao, Morrison John, Brenner Hermann, Chan Andrew, Gruber Stephen B., Keku Temitope, Li Li, Moreno Victor, Pellatt Andrew J, Peters Ulrike, Samadder N. Jewel, Schmit Stephanie L., Ulrich Cornelia M., Um Caroline, Wu Anna, Lewinger Juan Pablo, Drew David A., Mi Huaiyu

Primary Institution: University of Southern California

Hypothesis

Can pathway-defined polygenic risk scores (pPRS) improve the detection of gene-environment interactions compared to standard polygenic risk scores (PRS)?

Conclusion

The study found that pPRS significantly improved the detection of interactions between genetic risk and NSAID use in colorectal cancer compared to standard PRS.

Supporting Evidence

Pathway-defined PRS showed greater power in detecting interactions than standard PRS.
Significant pPRS × NSAIDs interaction was found in the TGF-β and GRHR pathways.
Regular NSAIDs use reduced CRC risk more significantly in individuals with high genetic risk.

Takeaway

This study shows that using special scores based on genetic pathways can help us understand how our genes and things we do, like taking medicine, work together to affect our health.

Methodology

The study used logistic regression to analyze interactions between polygenic risk scores and NSAID use in a large cohort of colorectal cancer patients.