期刊
BIOSTATISTICS
卷 13, 期 3, 页码 468-481出版社
OXFORD UNIV PRESS
DOI: 10.1093/biostatistics/kxr035
关键词
Causal inference; COPD; Family-based association; G-estimation; Gene-environment interaction
资金
- National Institutes of Health [NCRR] [P20RR020145, 5P20RR016481-10]
- IAP research network (Belgian government [Belgian Science Policy]) [P06/03]
- Ghent University
- Div Of Information & Intelligent Systems
- Direct For Computer & Info Scie & Enginr [1054631] Funding Source: National Science Foundation
- Emerging Frontiers
- Direct For Biological Sciences [850237] Funding Source: National Science Foundation
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.
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