A detailed description of materials and methods is given in Methods. The work-flow and organization of the project are given in Supplementary Fig. 16. Case series came from previously established collections with nationally representative recruitment: 2,000 samples were genotyped for each. The control samples came from two sources: half from the 1958 Birth Cohort and the remainder from a new UK Blood Service sample. The latter collection was established specifically for this study and is a UK national repository of anonymized DNA samples from 3,622 consenting blood donors. The vast majority of subjects were self-reported as of European Caucasian ancestry. All DNA samples were requantified and tested for degradation and PCR amplification. Genotyping was performed using GeneChip 500K arrays at the Affymetrix Services Lab (California): arrays not passing the 93% call rate threshold at P=0.33 with the Dynamic Model algorithm were repeated. CEL (cell intensity) files were transferred to WTCCC for quantile normalization, and genotypes called using a new genotyping algorithm, CHIAMO, developed for this project. QC/QA measures included sample call rate, overall heterozygosity and evidence of non-European ancestry (809