Recent GWAS studies have identified several new risk alleles for breast cancer [Easton et al., 2007; Hunter et al., 2007; Stacey et al., 2008; Gold et al., 2008]. Easton et al. [2007] conducted a two-stage GWAS in 4,398 breast cancer cases and 4,316 controls. They genotyped 227,876 SNPs in the first stage and selected 12,711 SNPs, approximately 5% of those typed in stage 1, to genotype in the second stage containing 3,990 invasive breast cancer cases and 3,916 controls. In the replication stage, they tested 30 SNPs that are either significant from the combined stage 1 and 2 data or are identified as candidate SNPs from other sources in 21,860 cases and 22,578 controls from 22 cohorts [Easton et al., 2007]. Nine SNPs showed associations in replication study with P < 0.05 with effects in the same direction as in stages 1 and 2. Under the assumption that the vast majority of 227,876 SNPs are from the null distribution, the 227,876 p-values of the difference in genotype frequency between cases and controls follow a distribution that similar to a uniform
