A sibling-augmented case-only approach for assessing multiplicative gene-environment interactions.

ABSTRACT: Family-based designs protect analyses of genetic effects from bias that is due to population stratification. Investigators have assumed that this robustness extends to assessments of gene-environment interaction. Unfortunately, this assumption fails for the common scenario in which the genotyped variant is related to risk through linkage with a causative allele. Bias also plagues other methods of assessment of gene-environment interaction. When testing against multiplicative joint effects, the case-only design offers excellent power, but it is invalid if genotype and exposure are correlated in the population. The authors describe 4 mechanisms that produce genotype-exposure dependence: exposure-related genetic population stratification, effects of family history on behavior, genotype effect

SUBMITTER: Weinberg CR 

PROVIDER: S-EPMC3246688 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature