We applied a recently developed multilocus association testing method (localized haplotype clustering) to Wellcome Trust Case
Control Consortium data (14,000 cases of seven common diseases and 3,000 shared controls genotyped on the Affymetrix 500 K
array). After rigorous data quality filtering, we identified three disease-associated loci with strong statistical support
from localized haplotype cluster tests but with only marginal significance in single marker tests. These loci are chromosomes
10p15.1 with type 1 diabetes (
p = 5.1 × 10
−9), 12q15 with type 2 diabetes (
p = 1.9 × 10
−7) and 15q26.2 with hypertension (
p = 2.8 × 10
−8). We also detected the association of chromosome 9p21.3 with type 2 diabetes (
p = 2.8 × 10
−8), although this locus did not pass our stringent genotype quality filters. The association of 10p15.1 with type 1 diabetes
and 9p21.3 with type 2 diabetes have both been replicated in other studies using independent data sets. Overall, localized
haplotype cluster analysis had better success detecting disease associated variants than a previous single-marker analysis
of imputed HapMap SNPs. We found that stringent application of quality score thresholds to genotype data substantially reduced
false-positive results arising from genotype error. In addition, we demonstrate that it is possible to simultaneously phase
16,000 individuals genotyped on genome-wide data (450 K markers) using the Beagle software package.