Sister haplotypes and recombination disequilibrium: A new Approach to identify associations of haplotypes with complicated diseases

Abstract

Abstract Haplotype-based association analysis has several advantages over single-SNP association analysis. However, to date all haplotype-disease associations have not excluded recombination interference among multiple loci and hence some results might be confounded by recombination interference. A ssociation of sister haplotypes with a complicated disease, based on recombination disequilibrium (RD) was presented. We convert DNA base language to genotype language to determine four pairs of sister haplotypes. After doing RD tests in control and case cohorts, one can construct a two-by-two contingent table with sister-haplotypes and a disease and perform Chi-square test for association between haplotypes and disease. Applying this method to a haplotype dataset of Alzheimer disease (AD), association of sister-haplotypes containing ApoE3/4 with risk for AD was identified under no RD. Haplotypes within genes IL-13 were not associated with risk for breast cancer in the case of no RD and no association of haplotypes in IL-17A gene with risk for coronary artery disease were detected without RD. The previously reported associations of haplotypes within these genes with risk for these diseases might be due to strong RD and/or inappropriate haplotype pairs.