Data were imputed for all scans for ~2.6 million SNPs with the HapMap version 2 CEU panel (Utah residents of Northern and Western European ancestry) as a reference, using the program MaCH v1.0. Imputation was conducted separately for each scan. Estimated per-allele ORs and standard errors were generated from the imputed genotypes using ProbABEL63. For two studies (UK2 and HEBCS), estimates were adjusted by the first three principal components, as this was found to materially reduce the inflation of test statistics. Residual inflation was then adjusted for by multiplying the variance by a genomic control adjustment factor, based on the ratio of the median χ2 test statistic to its expected value64. BBCS and UK2 used the same control data (WTCCC2) but different genotyping platforms. Data were imputed separately for these studies. For the combined analysis, the control set was divided randomly between the two studies, in proportion to the size of the case series, to provide disjoint strata. Overall significance tests for each SNP were performed using a fixed-effects meta-analysis; data were only included for a given study if the imputation accuracy r2 was >0.3.
