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.
Segurado
Ricardo
R
Biostatistics and Bioinformatics Unit and Department of Psychological Medicine, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK. segurador@cardiff.ac.uk
Hamshere
Marian L
ML
Glaser
Beate
B
Nikolov
Ivan
I
Moskvina
Valentina
V
Holmans
Peter A
PA