Parsimony would suggest that there is probably a graded influence of genetic variation in gene expression because for any gene many elements contribute to the control of its expression, and genetic variability in any one of such genes is likely to result in a change in expression. In this model, at any locus there are multiple variants, which can exist across a single haplotype block or in multiple haplotype blocks proximal to the affected transcript. Thus, there is no single haplotype for disease risk and no single protective haplotype but, rather, a collection of haplotypes that confer a graded risk of disease. The variant with the highest population attributable risk (a combination of allele frequency and relative risk) is likely to be the first at the locus to be detected as a risk factor, and further dissection of the same locus will yield other risk alleles of smaller effect. Although such dissection is proving to be a tough task, there are already examples of success. After the identification of a risk allele for macular degeneration, a polymorphism that causes the
