To assess the tendency of rare disease-causing variants to create synthetic signals of association that are credited to single polymorphisms that are much more common in the population than the causal variants, we have simulated 10,000 haplotypes based on a coalescent model in a region either with or without recombination (Materials and Methods). We assumed that gene variants that influence disease have an allele frequency between 0.005 and 0.02, which is generally below the range of reliable detection (either by inclusion or indirect representation) using the genome-wide association platforms currently in use. We assumed a baseline probability of disease of φ for individuals with none of the rare genetic risk factors. The presence of at least one rare risk allele at the locus increased the probability of disease from φ to γ. We considered two values of φ (0.01, 0.1) and chose values of the penetrance γ such that the genotypic relative risk (GRR) of the rare causal variants varied incrementally between 2 and 6, where GRR is the ratio γ/φ. These values were chosen to explore the space around
