Abstract
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.
Highlights
Problem 2 of Genetic Analysis Workshop 15 (GAW15) includes genome-wide genotyping of marker sets for linkage studies in rheumatoid arthritis (RA)
Marker maps Four data sets were analyzed for autosomal genetic linkage to RA (Table 1)
In cases in which several marker sets were available in the same sample, the most informative was selected as detailed below
Summary
Problem 2 of Genetic Analysis Workshop 15 (GAW15) includes genome-wide genotyping of marker sets for linkage studies in rheumatoid arthritis (RA). Four research groups contributed sets of markers across the genome genotyped in four independent pedigree samples. NARAC (North American Rheumatoid Arthritis Consortium) held by far the largest sample, consisting of multiplex families genotyped for 10-cM linkage mapping set and a panel of single-nucleotide polymorphisms (SNPs) genotyped by Illumina. A Canadian group provided pedigrees genotyped for the same Illumina marker panel as well as a dense 100 k Affymetrix SNP map. ECRAF (European Consortium on Rheumatoid Arthritis Families) genotyped a dense microsatellite panel. There was a United Kingdom (UK) data set, comprising both microsatellite and SNP markers with a two-stage design
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