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.
Collins
Andrew
A
Human Genetics Division, Southampton General Hospital, University of Southampton, School of Medicine, Duthie Building (MP808), Southampton, SO 16 6YD, UK. arc@soton.ac.uk.
Lau
Winston
W
Human Genetics Division, Southampton General Hospital, University of Southampton, School of Medicine, Duthie Building (MP808), Southampton, SO 16 6YD, UK.
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