TY - JOUR
T1 - A composite-likelihood approach for identifying polymorphisms that are potentially directly associated with disease
AU - Biernacka, Joanna M.
AU - Cordell, Heather J.
N1 - Funding Information:
This research was funded by the Wellcome Trust, grant reference 074524.
PY - 2009
Y1 - 2009
N2 - If a linkage signal can be fully accounted for by the association of a particular polymorphism with the disease, this polymorphism may be the sole causal variant in the region. On the other hand, if the linkage signal exceeds that explained by the association, different or additional directly associated loci must exist in the region. Several methods have been proposed for testing the hypothesis that association with a particular candidate single-nucleotide polymorphism (SNP) can explain an observed linkage signal. When several candidate SNPs exist, all of the existing methods test the hypothesis for each candidate SNP separately, by fitting the appropriate model for each individual candidate SNP. Here we propose a method that combines analyses of two or more candidate SNPs using a composite-likelihood approach. We use simulations to demonstrate that the proposed method can lead to substantial power increases over the earlier single SNP analyses.
AB - If a linkage signal can be fully accounted for by the association of a particular polymorphism with the disease, this polymorphism may be the sole causal variant in the region. On the other hand, if the linkage signal exceeds that explained by the association, different or additional directly associated loci must exist in the region. Several methods have been proposed for testing the hypothesis that association with a particular candidate single-nucleotide polymorphism (SNP) can explain an observed linkage signal. When several candidate SNPs exist, all of the existing methods test the hypothesis for each candidate SNP separately, by fitting the appropriate model for each individual candidate SNP. Here we propose a method that combines analyses of two or more candidate SNPs using a composite-likelihood approach. We use simulations to demonstrate that the proposed method can lead to substantial power increases over the earlier single SNP analyses.
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U2 - 10.1038/ejhg.2008.242
DO - 10.1038/ejhg.2008.242
M3 - Article
C2 - 19092770
AN - SCOPUS:67349287340
SN - 1018-4813
VL - 17
SP - 644
EP - 650
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 5
ER -