Genome-wide linkage disequilibrium mapping of hypertension in Japan.

Hypertension is a common, complex phenotype resulting from the interaction between genetic and environmental factors. To select candidate regions potentially responsible for hypertension, we are conducting a genome-wide linkage disequilibrium (LD) mapping of hypertension using dinucleotide repeat markers in 146 hypertensive and 136 normotensive subjects. Although the LD mapping is still underway, 19 alleles of 15 markers have already shown a nominally significant association (p<0.05), with odds ratios ranging from 0.08 to 5.12, suggesting the presence of many hypertension-related loci with weak effects in the human genome. These markers should be further assessed, adjusting for confounding factors and considering gene-gene and gene-environmental interactions in additional samples. In this report, we discuss our ongoing LD mapping project and describe the 15 markers thus far discovered. Among the 15 markers, D10S537 had a highly significant association with hypertension (p=5.3x10(-5); OR=3.80; 95% CI=1.98-7.27; where OR indicates the odds ratio and 95% CI indicates the 95% confidence interval). Further analysis in a large Japanese population showed that D10S537 was significantly associated with hypertension (p=0.044; OR=1.27; 95% CI=1.01-1.59). D10S537 was more significantly associated with hypertension in subjects with normotriglyceridemia in our population (p=0.007; OR=1.47; 95% CI=1.11-1.95).