the combined GWAS data set, 10,864 (51%) had effects in the same direction in the GWAS and iCOGS data, and, for these SNPs, inflation was 1.26 (λ1000 = 1.007) compared with 1.14 (λ1000 = 1.0035) for SNPs with effects in opposite directions in the two stages. A similar direction of effect was seen for these SNPs in the combined GWAS (λ = 0.87 for SNPs with effects in the same direction versus λ = 0.79 for SNPs with effects in the opposite direction, with inflation being <1 because SNPs showing evidence of association were excluded). Taken together, these results suggest that much of the inflation in the test statistics for SNPs not selected for breast cancer association is also due to the effect of true associations. Moreover, some of the excess of statistically significant associations seen in the SNPs not selected for breast cancer association was due to SNPs close to breast cancer–associated SNPs. For example, of the 45 SNPs with significant association at P < 0.00001, 21 were within 1 Mb of 1 of the newly identified breast cancer loci identified at our set genome-wide significance threshold. Taken together, these results strongly suggest that most of the excess of
