On the basis of the current set of loci and assuming that all loci combine multiplicatively, the currently known loci now define a genetic profile for which 5% of the female population has a risk that is ~2.3-fold higher than the population average and for which 1% of the population has a risk that is ~3-fold higher. However, the large excess of significant associations among the SNPs selected from the GWAS suggests that many more susceptibility loci exist that have not met our threshold for genome-wide-significant association in this study and that these explain a similar fraction of the heritability as the currently known loci. The observation, made by comparing effect sizes in the iCOGS stage with those in the GWAS, that a very large number of loci, perhaps several thousand, contribute to polygenic susceptibility to breast cancer is consistent with results from GWAS in other complex disorders such as schizophrenia, using a different analytical approach60. Incorporating these loci into risk models should substantially improve disease prediction, even if not all loci can be identified individually. Moreover, fine-scale mapping of
