Comparative study of family based haplotypic association methods

Evidence has been found for a gene for Reading Disability on chromosome 15q15 using family-based association mapping [1]. In the first stage of the study a two locus haplotype association was assessed for eight markers using HAPMAX [2], entailing a haplotype relative risk (HER) method, and TRANSMIT, representing a transmission/disequilibrium test (TDT). Both methods detected association, although not to the same extent. HAPMAX found eight pairwise combinations to be significant at levels less than 5%, whereas TRANSMIT found only two. Both of the latter were also significant with HAPMAX. The two significant combinations with TRANSMIT both included d15s994, the marker that was found to be highly significantly associated with Reading Disorder on its own, using HRR (p=0.007) and ETDT (p=0.004) on the same data set [1]. HAPMAX and TRANSMIT differ in their use of family information, and in extent to which they are robust to departures from Hardy Weinberg equilibrium.