A unifying approach for haplotype analysis of quantitative traits in family-based association studies: Testing and estimating gene-environment interactions with complex exposure variables

Publication Year:
2006
Usage 1036
Downloads 727
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Repository URL:
https://biostats.bepress.com/cobra/art11
Author(s):
Vansteelandt, Stijn; Lange, Christoph
Publisher(s):
bepress
Tags:
Genetics
article description
We propose robust and e±cient tests and estimators for gene-environment/gene-drug interactions in family-based association studies. The methodology is designed for studies in which haplotypes, quantitative pheno- types and complex exposure/treatment variables are analyzed. Using causal inference methodology, we derive family-based association tests and estimators for the genetic main effects and the interactions. The tests and estimators are robust against population admixture and strati¯cation without requiring adjustment for confounding variables. We illustrate the practical relevance of our approach by an application to a COPD study. The data analysis suggests a gene-environment interaction between a SNP in the Serpine gene and smok- ing status/pack years of smoking that reduces the FEV1 volume by about 0.02 liter per pack year of smoking. Simulation studies show that the pro- posed methodology is su±ciently powered for realistic sample sizes and that it provides valid tests and effect size estimators in the presence of admixture and stratification.