On the assumption that the risks conferred by common susceptibility loci combine multiplicatively (no interaction on a log-additive scale) and on the basis of the per-allele OR estimates from the iCOGS stage, we determined that the 41 newly associated loci explain approximately 5% of the familial risk of breast cancer. However, the overall excess of significant associations for SNPs selected from the breast cancer GWAS for genotyping in the iCOGS stage suggests that a much larger number of loci contribute to susceptibility, although they did not have associations reaching genome-wide levels of significance in the current study. To assess this hypothesis more formally, we identified a set of 10,668 SNPs selected from the GWAS that were uncorrelated (r2 < 0.1 between any pair). Of these, the estimated OR was in the same direction as in the combined GWAS for 5,918 SNPs and in the opposite direction for 4,750 SNPs. Assuming that SNPs with effects in opposite directions are not associated with risk, an estimated 1,168 loci selected from the GWAS are associated with risk. However, this is an underestimate because
