Note the similarity of the two equations. The terms of dc would add up to dh exactly, if the term f6 (g6−g)/2 that corresponds to the cis-heterozygote, Ab/aB, was replaced by the trans-heterozygote (AB/ab) term, f5 (g5−g)/2. When AB is a susceptibility haplotype, the term dh is positive, and so is dc. In other words, the haplotypic and the composite frequency differences are in the same direction for the ‘haplotype-driven’ models. We define haplotype-driven models to include recessive, dominant, as well as intermediate models, notably the additive model, where susceptibilities of AB heterozygotes are between those for the genotypes with 0 and 2 copies of AB. Whether the sign of dc is in the same direction as that for dh is determined by the magnitude of the terms that corresponds to the cis- and trans-genotypes, Ab/aB and AB/ab. The condition that the dc is non-negative is satisfied for the ‘haplotype-driven’ models because of the constraints on the population frequencies and the model susceptibilities. Consider the recessive model: g1 > g2; g2 = g3 … = g10. Under this model, the
