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Gene-environment interaction testing in family-based association studies with phenotypically ascertained samples: a causal inference approach

Journal Contribution - Journal Article

We propose a method for testing gene-environment (G x E) interactions on a complex trait in family-based studies in which a phenotypic ascertainment criterion has been imposed. This novel approach employs G-estimation, a semiparametric estimation technique from the causal inference literature, to avoid modeling of the association between the environmental exposure and the phenotype, to gain robustness against unmeasured confounding due to population substructure, and to acknowledge the ascertainment conditions. The proposed test allows for incomplete parental genotypes. It is compared by simulation studies to an analogous conditional likelihood-based approach and to the QBAT-I test, which also invokes the G-estimation principle but ignores ascertainment. We apply our approach to a study of chronic obstructive pulmonary disorder.
ISSN: 1465-4644
Issue: 3
Volume: 13
Pages: 468 - 481
Publication year:2012
BOF-publication weight:6
CSS-citation score:1
Authors from:Higher Education