Comparison of genome-wide single-nucleotide polymorphism linkage analyses in Caucasian and Hispanic NARAC families

We performed linkage analysis on families with rheumatoid arthritis, stratifying by ethnic origin. We compared results using either Kong and Cox nonparametric LOD scores or MOD score analysis using the software GeneHunter MODSCORE. We first applied SNPLINK to remove markers showing excess linkage disequilibrium from the SNPs in the Illumina IV SNP Linkage panel. In this analysis there were 659 self-reported Caucasian families and 29 self-reported Hispanic families in the NARAC collection. Chromosome 19 yielded MOD scores > 3.00 in the Hispanic group, while chromosomes 2, 6, 7, 11, and XY had MOD scores > 3.00 in the Caucasian group. We performed simulation studies to evaluate the empirical distribution of the MOD score for autosomal loci separately in Hispanics and Caucasians. Results showed genome-wide significant evidence for linkage in Caucasians for chromosomes 2q and 6p, but no significant evidence for any linkages in the Hispanics, including little evidence for linkage to chromosome 6p in this group. An examination of the difference of phenotypes in two ethnic groups suggested significantly earlier mean age of onset, higher percentage of anti-cyclic citrullinated peptide positive people, and lower percentage of affected people carrying shared epitopes in Hispanics than those in Caucasians. A larger sample size of the Hispanic group is needed to identify linkage regions.