The alleles of multiple markers transmitted from one parent are called a haplotype. Haplotype analysis of safety and efficacy data can incorporate the information from multiple markers from the same gene or genes, which are physically close on a specific chromosome. Genotypic data from unrelated individuals do not contain information on which alleles were transmitted from each parent, but haplotype frequencies can be estimated using several existing methodologies such as the expectation maximization (EM) algorithm. Using a novel methodology, haplotype trend regression, it is possible to associate disease or drug response with haplotype frequencies of individuals.

Briefly, haplotype trend regression takes a series of marker genotypes, estimates overall haplotype frequencies and computes haplotype probabilities for each observation using either the composite haplotype method (26.7) or the expectation maximization (EM) algorithm, and forms a linear regression on the response using the haplotype probabilities as the regression matrix. First we discuss the composite haplotype method (26.7) of computing haplotype frequencies, then we describe haplotype trend regression.