CHROMSCAN: genome-wide association using a linkage disequilibrium map.
CHROMSCAN implements a composite likelihood model for the analysis of association data. Disease-gene localisation is on a linkage disequilibrium unit (LDU) map, and locations and standard errors, for putatively causal polymorphisms, are determined by the programme. Distortions of the probability distribution created by auto-correlation are avoided by implementation of a permutation test. We evaluated the relative efficiency of the LDU map by simulating pseudo-phenotypes in real genotype samples. We observed that multi-locus mapping on an underlying LDU map reduces location error by approximately 46%. Furthermore, there is a small, but significant, increase in power of approximately 5%. Effective meta-analysis across multiple samples, increasingly important to combine evidence from genome-wide and other association data, is achieved through the weighted combination of location evidence provided by the programme.
Human Genetics Division, Southampton General Hospital, University of Southampton, School of Medicine, Duthie Building (MP808), Southampton, SO 16 6YD, UK. arc@soton.ac.uk.
Andrew
A
Collins
Human Genetics Division, Southampton General Hospital, University of Southampton, School of Medicine, Duthie Building (MP808), Southampton, SO 16 6YD, UK.
Winston
W
Lau
D016022:Case-Control Studies; D002874:Chromosome Mapping; D003198:Computer Simulation; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D005819:Genetic Markers