Genome-wide association studies using single-nucleotide polymorphisms versus haplotypes: an empirical comparison with data from the North American Rheumatoid Arthritis Consortium.
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.
Shim
Heejung
H
Department of Statistics, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706 USA.
Chun
Hyonho
H
Department of Statistics, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706 USA.
Engelman
Corinne D
CD
Department of Population Health Sciences, University of Wisconsin-Madison, 707 WARF Building, 610 North Walnut Street, Madison, Wisconsin 53726 USA.
Payseur
Bret A
BA
Laboratory of Genetics, University of Wisconsin-Madison, 425-G Henry Mall, Madison, Wisconsin 53706 USA.