Estimating genetic effect sizes under joint disease-endophenotype models in presence of gene-environment interactions.

ABSTRACT: Effects of genetic variants on the risk of complex diseases estimated from association studies are typically small. Nonetheless, variants may have important effects in presence of specific levels of environmental exposures, and when a trait related to the disease (endophenotype) is either normal or impaired. We propose polytomous and transition models to represent the relationship between disease, endophenotype, genotype and environmental exposure in family studies. Model coefficients were estimated using generalized estimating equations and were used to derive gene-environment interaction effects and genotype effects at specific levels of exposure. In a simulation study, estimates of the effect of a genetic variant were substantially higher when both an endophenotype and an environmental

SUBMITTER: Bureau A 

PROVIDER: S-EPMC4516976 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature