NDLI: The Impact of Incomplete Linkage Disequilibrium and Genetic Model Choice on the Analysis and Interpretation of Genome-wide Association Studies

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The Impact of Incomplete Linkage Disequilibrium and Genetic Model Choice on the Analysis and Interpretation of Genome-wide Association Studies

Content Provider	PubMed Central
Author	Iles, Mark M.
Abstract	When conducting a genetic association study, it has previously been observed that a multiplicative risk model tends to fit better at a disease-associated marker locus than at the ungenotyped causative locus. This suggests that, while overall risk decreases as linkage disequilibrium breaks down, non-multiplicative components are more affected. This effect is investigated here, in particular the practical consequences it has on testing for trait/marker associations and the estimation of mode of inheritance and risk once an associated locus has been found. The extreme significance levels required for genome-wide association studies define a restricted range of detectable allele frequencies and effect sizes. For such parameters there is little to be gained by using a test that models the correct mode of inheritance rather than the multiplicative; thus the Cochran-Armitage trend test, which assumes a multiplicative model, is preferable to a more general model as it uses fewer degrees of freedom. Equally when estimating risk, it is likely that a multiplicative risk model will provide a good fit to the data, regardless of the underlying mode of inheritance at the true susceptibility locus. This may lead to problems in interpreting risk estimates.
Related Links	http://dx.doi.org/10.1111/j.1469-1809.2010.00579.x
Ending Page	379
Page Count	5
Starting Page	375
File Format	PDF
ISSN	00034800
e-ISSN	14691809
Journal	Annals of Human Genetics
Issue Number	4
Volume Number	74
Language	English
Publisher	Blackwell Publishing Ltd
Publisher Date	2010-06-01
Access Restriction	Open
Rights Holder	Blackwell Publishing Ltd
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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