Affymetrix Expression Console was used to process raw data. All probes, which contain common SNPs (MAF ≥ 0.01) based on the 1000 Genome Project data and HapMap data, or could be mapped to multiple genomic regions, were excluded from the analysis. ComBat 18 was used to correct for batch effects within the methylation and expression array data. For later analysis of each technical replicate pair, the data were averaged for the replicated samples to obtain a single datum. In order to remove the effects of known and unknown covariates on the data, surrogate variable analysis (SVA) 19 was applied and the identified surrogate variables were regressed out. We have found that these methods perform well in removing the effects of batch and known covariates such as pH. To fit a normal distribution, quantile normalization was used for both expression and methylation residuals.
