Gene-by-Environment Interactions in Studies Based on Nuclear Families

• Activity Number: 564
• Type: Topic Contributed
• Date/Time: Wednesday, August 4, 2010 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Clarice R. Weinberg and Min Shi*+ and David Umbach
• Companies: National Institute of Environmental Health Sciences and National Institute of Environmental Health Sciences and National Institute of Environmental Health Sciences
• Keywords: gene-environment interaction ; case-parents designs ; discordant sib-pairs ; nuclear families

Abstract

Several proposed methods for examining haplotype-exposure interactions use data from affected individuals and their parents. Unfortunately, that design cannot assess the effects of exposure, limiting the interpretability of identified interactions. Motivated by the Two Sister Study, an ongoing study of families affected by young-onset breast cancer, we propose a new design that supplements the case-parents design with an unaffected sibling who is not genotyped but provides exposure data. This tetrad structure permits the study of haplotype effects, exposure effects, and haplotype-exposure interactions. We present findings from simulation studies to compare the performance of the tetrad design with the case-parents and the discordant sib-pairs designs in testing haplotype-exposure interaction. We compare both type I error rates and power under a range of scenarios.