Using Pathway Polygenic Risk Scores to Study Gene-Environment Interactions
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: Cold Spring Harbor Laboratory
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 pathway-defined PRS can significantly enhance the detection of interactions with environmental factors, particularly in colorectal cancer risk associated with NSAIDs.
Supporting Evidence
- Pathway-defined PRS can yield greater power in detecting gene-environment interactions.
- The study identified a significant interaction between pPRS and NSAIDs in colorectal cancer risk.
- Individuals with high genetic risk showed a stronger protective effect from NSAIDs.
Takeaway
This study shows that looking at specific gene pathways can help us understand how our genes and the environment work together to affect our health.
Methodology
The study used simulation to compare the power of detecting interactions using pPRS versus standard PRS and analyzed a large dataset of colorectal cancer cases.
Participant Demographics
The study analyzed data from 78,253 individuals with colorectal cancer.
Statistical Information
P-Value
0.0003
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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