The association between each SNP and breast cancer risk was tested using a 1-degree-of-freedom trend test adjusted for study and seven principal components (Online Methods). There was some evidence for inflation in the test statistics, detected using data from 22,897 uncorrelated SNPs on iCOGS not selected on the basis of breast cancer risk (λ = 1.20, λ1000 = 1.005; Supplementary Fig. 1a). There was, however, clear evidence of an excess of statistically significant associations among the SNPs selected from the GWAS analysis (Table 1 and Supplementary Fig. 1b). Although some excess was also observed among the SNPs not selected from the breast cancer GWAS, the excess of statistically significant associations was much more marked among the GWAS SNPs at all levels of statistical significance. In addition, of 21,128 SNPs not selected for breast cancer association that were also present in 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
