Design and sample-size considerations in the detection of linkage disequilibrium with a disease locus.
The presence of linkage disequilibrium between closely linked loci can aid in the fine mapping of disease loci. We investigate the power of several designs for sampling individuals with different disease genotypes. As expected, haplotype data provide the greatest power for detecting disequilibrium, but, in the absence of parental information to resolve the phase of double heterozygotes, the most powerful design samples only individuals homozygous at the trait locus. For rare diseases, such a scheme is generally not feasible, and we also provide power and sample-size calculations for designs that sample heterozygotes. The results provide information useful in planning disequilibrium studies.
Olson
J M
JM
Department of Biostatistics, University of Washington, Seattle.
Wijsman
E M
EM
D002874:Chromosome Mapping / Q000379:methods*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015203:Reproducibility of Results; D012107:Research Design; D012494:Sampling Studies