As can be seen in Figure 2, for GRR=1.2 the number of cases and controls needed to detect a causative allele reduces from about 23,000 at minor allele frequency (MAF) =5% to ~ 8,000 at MAF=20% and to ~6,000 at MAF=40%. The effect of GRR on the study size is even greater: at MAF =10% and GRR 1.1, about 47,000 cases and controls are needed, but as GRR increases to 1.2, 1.3, 1.5, 1.7, and 2.0 the required number of individuals decreases to ~12,500, ~6,000, 2,300, 1,300, and 700 respectively. For instance, a GWAS for age-related macular degeneration (AMD) of only 96 cases and 50 controls was able to detect an association with a common variant in the complement factor H gene (CFH) at a nominal P value <10−7 [101]. The power to detect this association was due to the high GRR caused by CFH variant: the presence of two risk alleles in an individual increased risk of developing AMD by a factor of 7.4 [101]. On the other hand, in order to detect alleles with modest effect sizes, tens
