Family-based gene-by-environment interaction studies: revelations and remedies.

ABSTRACT: Bias can arise in case-control studies of genotype effects if the underlying population is structured (genetically stratified or admixed). Nuclear-family-based studies enjoy robustness against such bias, provided that inference conditions properly on the parents. Investigators have extended family-based methods to study gene-by-environment interactions, regarding such extensions as retaining robustness. We demonstrate via simulations that, if population structure involves the exposure, nuclear-family-based analyses of gene-by-exposure interaction remain vulnerable to inflated Type I error rates through subtle dependencies that investigators have failed to appreciate. Motivated by the Two Sister Study, an ongoing study of families affected by young-onset breast cancer, we consider a design

SUBMITTER: Shi M 

PROVIDER: S-EPMC3132804 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature