Fine-scale mapping in case-control samples using locus scoring and haplotype-sharing methods.
Both haplotype-based and locus-based methods have been proposed as the most powerful methods to employ when fine mapping by association. Although haplotype-based methods utilize more information, they may lose power as a result of overparameterization, given the large number of haplotypes possible over even a few loci. Recently methods have been developed that cluster haplotypes with similar structure in the hope that this reflects shared genealogical ancestry. The aim is to reduce the number of parameters while retaining the genotype information relating to disease susceptibility. We have compared several haplotype-based methods with locus-based methods. We utilized 2 regions (D2 and D4) simulated to be in linkage disequilibrium and to be associated with disease susceptibility, combining 5 replicates at a time to produce 4 datasets that were analyzed. We found little difference in the performance of the haplotype-based methods and the locus-based methods in this dataset.
Humphreys
Keith
K
Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, S-171 77 Stockholm, Sweden. keith.humphreys@meb.ki.se
Iles
Mark M
MM
D016022:Case-Control Studies; D056426:Genetic Loci / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020161:Physical Chromosome Mapping / Q000379:methods*