Efficacy assessment of SNP sets for genome-wide disease association studies.
The power of a genome-wide disease association study depends critically upon the properties of the marker set used, particularly the number and physical spacing of markers, and the level of inter-marker association due to linkage disequilibrium. Extending our previously devised theoretical framework for the entropy-based selection of genetic markers, we have developed a local measure of the efficacy of a marker set, relative to including a maximally polymorphic single nucleotide polymorphism (SNP) at the map position of interest. Using this quantitative criterion, we evaluated five currently available SNP sets, namely Affymetrix 100K and 500K, and Illumina 100K, 300K and 550K in the CEU, YRI and JPT + CHB HapMap populations. At 50% relative efficacy, the commercial marker sets cover between 19 and 68% of the human genome, depending upon the population under study. An optimal technology-independent 500K marker set constructed from HapMap for Caucasians, in contrast, would achieve 73% coverage at the same relative efficacy.
Wollstein
Andreas
A
Cologne Center for Genomics, Cologne, Germany.
Herrmann
Alexander
A
Wittig
Michael
M
Nothnagel
Michael
M
Franke
Andre
A
Nürnberg
Peter
P
Schreiber
Stefan
S
Krawczak
Michael
M
Hampe
Jochen
J
D002874:Chromosome Mapping / Q000379:methods*; D019277:Entropy; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005819:Genetic Markers; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide
D005819:Genetic Markers