Genome-wide association studies using single-nucleotide polymorphisms versus haplotypes: an empirical comparison with data from the North American Rheumatoid Arthritis Consortium

Abstract

The high genomic density of the single-nucleotide polymorphism (SNP) sets that are typically surveyed in genome-wide association studies (GWAS) now allows the application of haplotype-based methods. Although the choice of haplotype-based vs. individual-SNP approaches is expected to affect the results of association studies, few empirical comparisons of method performance have been reported on the genome-wide scale in the same set of individuals. To measure the relative ability of the two strategies to detect associations, we used a large dataset from the North American Rheumatoid Arthritis Consortium to: 1) partition the genome into haplotype blocks, 2) associate haplotypes with disease, and 3) compare the results with individual-SNP association mapping. Although some associations were shared across methods, each approach uniquely identified several strong candidate regions. Our results suggest that the application of both haplotype-based and individual-SNP testing to GWAS should be adopted as a routine procedure.

Figure 1

A comparison of haplotype and individual association tests on HLA region. -Log₁₀ transformed p-values are plotted across chromosomal location 32 Mbp to 33 Mbp. The results from individual association tests are represented by solid blue sticks; the results from haplotype association tests with GAB blocks are represented by dotted black lines.