LBC DNA-Methylation Quality Control
Details of DNA extraction and methylation profiling are described elsewhere.23 Background correction of the raw intensity data and generation of the methylation beta values were done with the R minfi package. Quality-control (QC) steps included the removal of probes with a low (<95%) detection rate at p < 0.01. Array control probes were inspected manually, and low-quality samples (e.g., samples with inadequate hybridization, bisulfite conversion, nucleotide extension, or staining signal) were removed. Samples with a low call rate according to the Illumina-based threshold (samples with <450,000 probes detected at p < 0.01) were removed. LBC samples had been genotyped with the Illumina 610-Quadv1 genotyping platform. Genotype information from the 65 SNP control CpG probes on the methylation chip were cross-validated with those from the genotyping chip with the R wateRmelon package. Where there was low correspondence, samples were excluded (n = 9). We also excluded eight participants whose reported sex did not match their predicted sex according to methylation levels for probes on the X and Y chromosomes.