Genotyping and quality control

Genotyping was carried out as part of a collaboration between BCAC and three other consortia (the Collaborative Oncological Gene-environment Study, COGS). Full details of SNP selection, array design, genotyping and post-genotyping quality control (QC) have been published [35]. Briefly, three categories of SNPs were chosen for inclusion on the array: (i) SNPs selected on the basis of pooled GWAS data, (ii) SNPs selected for the fine-mapping of published risk loci and (iii) candidate SNPs selected on the basis of previous analyses or specific hypotheses. The 313 SNPs described in the current study were candidate SNPs selected on the basis of the hypothesis that regulatory variants are involved in breast cancer susceptibility. In general, only SNPs with an Illumina design score of 0.8 or greater were considered. SNPs were preferentially accepted if they had a design score of 1.1 (i.e. had previously been genotyped on an Illumina platform). If not, we sought SNPs with r² = 1 with the selected SNP, and selected the SNP with the best design score. If no such SNP was available, we selected SNPs with r² > 0.8 with the chosen SNP, and selected the SNP with the best design score. For the COGS project overall, genotyping of 211,155 SNPs in samples was conducted using a custom Illumina Infinium array (iCOGS) in four centers. Genotypes were called using Illumina's proprietary GenCall algorithm. Standard quality control measures were applied across all SNPs and all samples genotyped as part of the COGS project [35]. After quality control, genotype data were available for 48 155 breast cancer cases and 43 612 controls, and call rates for all SNPs were > 95%.