In Figure 3 we show the minimum fold increase in genetic variance at a single causal locus compared to the genetic variance explained at a genotyped locus with a given RAF, for causal variants with allele frequencies of 0.005–0.05; the relationship is 1/r 2 (where r 2 is a measure of LD between the variants, see Box 2). The maximum r 2 (see Box 2) between a rare causal variant and SNPs typically included on GWAS chips is very low (Table 1). For example, when the frequency of an associated SNP allele is in the range of 0.2 to 0.5, the variation contributed by a causal variant of frequency 0.01 is at least 25 to 100 times larger than that detected at the genotyped SNP. In case-control studies, we can calculate the odds ratio at the causal variant that would be needed to generate the odds ratio detected at the genotyped SNP, which depends on the allele frequencies at the two loci (see Box 3). When the frequency of an associated SNP allele is in the range of 0.2 to
