Adjusting for Spurious Gene-by-Environment Interaction Using Case-Parent Triads
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Ji-Hyung Shin
In the case-parent trio design, unrelated children affected with a disease are genotyped along with their parents. Information may also be collected on environmental factors in the children. The design permits estimation and testing of genetic effects and gene-by-environment interaction. Recently, it has been demonstrated that when genotypes are measured at a non-causal test locus, population stratification can create spurious interaction. That is, the environmental factor can appear to modify the disease risk associated with genotypes at the test locus without modifying the disease risk of genotypes at the causal locus. One design-based approach that is robust to spurious interaction requires the environmental factor to also be available on an unaffected sibling of the affected child. We explore the source of spurious interaction and suggest an alternate approach that mitigates its effects using case-parent triads. Our approach is based on adjusting the risk model using ancestry informative markers or random markers measured on the affected child and does not require data on unaffected siblings. We apply an approach to generating case-parent data, implemented in a freely-available R package soon to be released on the Comprehensive R Archive Network (CRAN).
©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
Articles in the same Issue
- Editorial Introduction
- Special Issue on Computational Statistical Methods for Genomics and Systems Biology
- Article
- A Generalized Hidden Markov Model for Determining Sequence-based Predictors of Nucleosome Positioning
- Gene Filtering in the Analysis of Illumina Microarray Experiments
- Principal Components of Heritability for High Dimension Quantitative Traits and General Pedigrees
- Bayesian Sparsity-Path-Analysis of Genetic Association Signal using Generalized t Priors
- A Family-Based Probabilistic Method for Capturing De Novo Mutations from High-Throughput Short-Read Sequencing Data
- Adjusting for Spurious Gene-by-Environment Interaction Using Case-Parent Triads
- Querying Genomic Databases: Refining the Connectivity Map
- A Model-Based Analysis to Infer the Functional Content of a Gene List
- Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate
- Improving Pedigree-based Linkage Analysis by Estimating Coancestry Among Families
Articles in the same Issue
- Editorial Introduction
- Special Issue on Computational Statistical Methods for Genomics and Systems Biology
- Article
- A Generalized Hidden Markov Model for Determining Sequence-based Predictors of Nucleosome Positioning
- Gene Filtering in the Analysis of Illumina Microarray Experiments
- Principal Components of Heritability for High Dimension Quantitative Traits and General Pedigrees
- Bayesian Sparsity-Path-Analysis of Genetic Association Signal using Generalized t Priors
- A Family-Based Probabilistic Method for Capturing De Novo Mutations from High-Throughput Short-Read Sequencing Data
- Adjusting for Spurious Gene-by-Environment Interaction Using Case-Parent Triads
- Querying Genomic Databases: Refining the Connectivity Map
- A Model-Based Analysis to Infer the Functional Content of a Gene List
- Candidate Pathway Based Analysis for Cleft Lip with or without Cleft Palate
- Improving Pedigree-based Linkage Analysis by Estimating Coancestry Among Families
