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A Simple Loglinear Model for Haplotype Effects in a Case-Control Study Involving Two Unphased Genotypes
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Stuart G. Baker
Published/Copyright:
June 2, 2005
Because haplotypes may parsimoniously summarize the effect of genes on disease, there is great interest in using haplotypes in case-control studies of unphased genotype data. Previous methods for investigating haplotypes effects in case-control studies have not allowed for both of the following two scenarios that could have a large impact on results (i) departures from Hardy-Weinberg equilibrium in controls as well as cases, and (ii) an interactive effect of haplotypes and environmental covariates on the probability of disease. A new method is proposed that generalizes the model of Epstein and Satten to incorporate both (i) and (ii). Computations are relatively simple involving a single loglinear design matrix for parameters modeling the distribution of haplotype frequencies in controls, parameters modeling the effect of haplotypes and covariate-haplotype interactions on disease, and nuisance parameters required for correct inference. Based on simulations with realistic sample sizes, the method is recommended with data from two genotypes, a recessive or dominant model linking haplotypes to disease, and estimates of haplotype effects among haplotypes with a frequency greater than 10%. The methodology is most useful with candidate genotype pairs or for searching through pairs of genotypes when scenarios (i) and (ii) are likely. An example without a covariate illustrates the importance of modeling a departure from Hardy-Weinberg equilibrium in controls.
Keywords: Composite Linear Model; EM algorithm; Gene-environment interaction; Genetics; Multinomial-Poisson transformation; Newton-Raphson
Published Online: 2005-6-2
©2011 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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Keywords for this article
Composite Linear Model;
EM algorithm;
Gene-environment interaction;
Genetics;
Multinomial-Poisson transformation;
Newton-Raphson
Articles in the same Issue
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- Estimating Motifs Under Order Restrictions
- Reproducible Research: A Bioinformatics Case Study
- Generalized Rank Tests for Replicated Microarray Data
- Stepwise Normalization of Two-Channel Spotted Microarrays
- Comparing Automatic and Manual Image Processing in FLARE Assay Analysis for Colon Carcinogenesis
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