The haplotype linkage disequilibrium test for genome-wide screens: its power and study design.

The focus of human genetics continues to shift toward the dissection of complex phenotypes. Integral to these endeavors is the development of powerful analytical tools. To this end, we propose a novel method designated the haplotype linkage disequibrium (LD) test for identifying diseases genes. The basic structure of the haplotype test statistic is a chi-square in which haplotypes, as opposed to individual marker data, are compared between cases and controls. Specifically, we performed power calculations and demonstrate that the use of haplotypes improves the power of mapping disease genes. We show that this approach can be used for initial genome-wide screens in mapping disease genes. Furthermore, we investigated the factors influencing statistical power of the method and discussed basic principals underlying study design. Published data from the Hereditary Hemochromatosis region was used to illustrate the utility of the haplotype test. Also discussed is its relationship with linkage disequibrium.