Article

Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals.

GlaxoSmithKline Inc., Discovery Genetics, Research Triangle Park, NC 27709, USA.
Human Heredity (impact factor: 1.79). 02/2002; 53(2):79-91. DOI:57986 pp.79-91
Source: PubMed

ABSTRACT There have been increasing efforts to relate drug efficacy and disease predisposition with genetic polymorphisms. We present statistical tests for association of haplotype frequencies with discrete and continuous traits in samples of unrelated individuals. Haplotype frequencies are estimated through the expectation-maximization algorithm, and each individual in the sample is expanded into all possible haplotype configurations with corresponding probabilities, conditional on their genotype. A regression-based approach is then used to relate inferred haplotype probabilities to the response. The relationship of this technique to commonly used approaches developed for case-control data is discussed. We confirm the proper size of the test under H(0) and find an increase in power under the alternative by comparing test results using inferred haplotypes with single-marker tests using simulated data. More importantly, analysis of real data comprised of a dense map of single nucleotide polymorphisms spaced along a 12-cM chromosomal region allows us to confirm the utility of the haplotype approach as well as the validity and usefulness of the proposed statistical technique. The method appears to be successful in relating data from multiple, correlated markers to response.

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Keywords

approaches
 
case-control data
 
continuous traits
 
correlated markers
 
drug efficacy
 
expectation-maximization algorithm
 
genetic polymorphisms
 
genotype
 
haplotype approach
 
possible haplotype configurations
 
proper size
 
proposed statistical technique
 
real data
 
regression-based approach
 
samples
 
simulated data
 
single nucleotide polymorphisms spaced
 
single-marker tests
 
test results
 
unrelated individuals