A score test for genetic class-level association with nonlinear biomarker trajectories

Area of Science:

• Genomics
• Immunology
• Biostatistics

Background:

• Genetic regulation of biological responses to inflammatory stress may differ from homeostatic control.
• Understanding these differences is crucial for personalized medicine and disease management.

Purpose of the Study:

• To test the hypothesis that genetic regulation differs between inflammatory response and homeostatic control.
• To identify genetic loci associated with longitudinal biomarker trajectories during inflammatory stimulus.

Main Methods:

• Employed a single-SNP score test and a novel class-level testing strategy for longitudinal data.
• Utilized a class-level association score statistic accounting for linkage disequilibrium.
• Applied methods to biomarker data from the Genetics of Evoked Responses to Niacin and Endotoxemia study.

Main Results:

• Results suggest a distinct genetic basis for evoked inflammatory responses compared to resting state.
• Identified several potentially novel genetic loci associated with dynamic biomarker changes.
• Demonstrated appropriate type-1 error rate control, computational efficiency, and statistical power in simulations.

Conclusions:

• The genetic underpinnings of dynamic biological responses to inflammatory stimuli are different from those governing homeostatic states.
• The developed methods are effective for identifying genetic associations in longitudinal biomarker data.
• Findings contribute to understanding the genetic architecture of inflammatory and metabolic responses.