The relations shown in figure 2 and the web figure illustrate one reason for the poor predictive performance of a panel of single nucleotide polymorphisms associated with common diseases. Although people carrying multiple risk alleles are at more extreme risk of type 2 diabetes than those carrying fewer copies, they represent only a small proportion of the population, because the inheritance of each risk allele is an independent event—the probability of inheriting multiple risk alleles is a function of the frequency of each allele in the population. For example, the probability of inheriting 10 independent risk alleles with frequencies around 0.3 is 0.310 (about 6×10−6). People with an intermediate number of risk alleles would therefore be expected to account for the major portion of cases of type 2 diabetes, because of the large number of people at intermediate risk in the population. This explains the substantial overlap of the distribution of risk alleles among people who developed diabetes and those who remained disease-free, which makes it difficult to set a cut-off point of a gene count (or genetic risk function)
