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

(2012) BIOSTATISTICS. 13(3). p.468-481
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Bioinformatics: from nucleotids to networks (N2N)
Abstract
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.
Keywords
Causal inference, COPD, Family-based association, G-estimation, Gene-environment interaction, OBSTRUCTIVE PULMONARY-DISEASE, CASE-PARENT TRIADS, POPULATION ADMIXTURE, RANDOMIZED-TRIALS, UNIFIED FRAMEWORK, GENOTYPE, EXPOSURE, TRAITS, DESIGN, RISK

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Citation

Please use this url to cite or link to this publication:

Chicago
Fardo, David W, Jinze Liu, Dawn L Demeo, Edwin K Silverman, and Stijn Vansteelandt. 2012. “Gene-environment Interaction Testing in Family-based Association Studies with Phenotypically Ascertained Samples: a Causal Inference Approach.” Biostatistics 13 (3): 468–481.
APA
Fardo, D. W., Liu, J., Demeo, D. L., Silverman, E. K., & Vansteelandt, S. (2012). Gene-environment interaction testing in family-based association studies with phenotypically ascertained samples: a causal inference approach. BIOSTATISTICS, 13(3), 468–481.
Vancouver
1.
Fardo DW, Liu J, Demeo DL, Silverman EK, Vansteelandt S. Gene-environment interaction testing in family-based association studies with phenotypically ascertained samples: a causal inference approach. BIOSTATISTICS. 2012;13(3):468–81.
MLA
Fardo, David W, Jinze Liu, Dawn L Demeo, et al. “Gene-environment Interaction Testing in Family-based Association Studies with Phenotypically Ascertained Samples: a Causal Inference Approach.” BIOSTATISTICS 13.3 (2012): 468–481. Print.
@article{3167754,
  abstract     = {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.},
  author       = {Fardo, David W and Liu, Jinze and Demeo, Dawn L and Silverman, Edwin K and Vansteelandt, Stijn},
  issn         = {1465-4644},
  journal      = {BIOSTATISTICS},
  language     = {eng},
  number       = {3},
  pages        = {468--481},
  title        = {Gene-environment interaction testing in family-based association studies with phenotypically ascertained samples: a causal inference approach},
  url          = {http://dx.doi.org/10.1093/biostatistics/kxr035},
  volume       = {13},
  year         = {2012},
}

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