Combining linkage data sets for meta-analysis and mega-analysis: the GAW15 rheumatoid arthritis data set
We have used the genome-wide marker genotypes from Genetic Analysis Workshop 15 Problem
2 to explore joint evidence for genetic linkage to rheumatoid arthritis across several samples. The
data consisted of four high-density genome scans on samples selected for rheumatoid arthritis. We
cleaned the data, removed intermarker linkage disequilibrium, and assembled the samples onto a
common genetic map using genome sequence positions as a reference for map interpolation. The
individual studies were combined first at the genotype level (mega-analysis) prior to a multipoint
linkage analysis on the combined sample, and second using the genome scan meta-analysis method
after linkage analysis of each sample. The two approaches were compared, and give strong support
to the HLA locus on chromosome 6 as a susceptibility locus. Other regions of interest include loci
on chromosomes 11, 2, and 12.
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