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Lookup NU author(s): Professor Heather Cordell
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Estimation and testing of genetic effects (genotype relative risks) are often performed conditionally on parental genotypes, using data from case-parent trios. This strategy avoids having to estimate nuisance parameters such as parental mating type frequencies, and also avoids generating spurious results due to confounding causes of association such as population stratification. For effects at a single locus, the resulting analysis is equivalent to matched case/control analysis via conditional logistic regression, using the case and three "pseudocontrols" derived from the untransmitted parental alleles. We previously showed that a similar approach can be used for analyzing genotype and haplotype effects at a set of closely linked loci, but with a required adjustment to the conditioning argument that results in varying numbers of pseudocontrols, depending on the disease model that is to be fitted. Here we extend this method to include the analysis of epistatic effects (gene-gene interactions) at unlinked loci, to include parent-of-origin effects at one or more loci, and to allow additional incorporation of gene-environment interactions. The conditional logistic approach provides a natural and flexible framework for incorporating these additional effects. By relaxing the conditioning on parental genotypes to allow exchangeability of parental genotypes, we show how the power of this approach can be increased when studying parent-of-origin effects. Simulations suggest that there is limited power to distinguish between parent-of-origin effects and effects due to interaction between genotypes of mother and child.
Author(s): Cordell HJ, Barratt BJ, Clayton DG
Publication type: Article
Publication status: Published
Journal: Genetic Epidemiology
Year: 2004
Volume: 26
Issue: 3
Pages: 167-185
Print publication date: 01/04/2004
ISSN (print): 0741-0395
ISSN (electronic): 1098-2272
Publisher: Wiley-Liss, Inc
URL: http://dx.doi.org/10.1002/gepi.10307
DOI: 10.1002/gepi.10307
Notes: 0741-0395 (Print) Journal Article
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