DNA was isolated from whole blood using the AutoPure LS system (Qiagen, Inc.), and then bisulfite-converted using the EZ DNA Methylation Gold kit (Zymo, Irvine, CA). To quantify DNA methylation at each site, we used beta values, as determined with the HumanMethylation450 BeadChip (Illumina, Inc.), which targets over 485,000 CpG sites at single-nucleotide resolution, and the iScan Reader (Illumina, Inc.). The ChAMP program (Morris et al., 2014 (link)) in BioConductor was used to initially process the data, using the default import settings. These included removal of methylation probes with a detection p-value less than 0.01, a beadcount less than three, and on the X or Y chromosome. To adjust for the two distinct Infinium assays that are simultaneously measured on this microarray (Infinium I and Infinium II), we used the champ.norm command with BMIQ normalization (Teschendorff et al., 2013 (link)). The BMIQ-normalized data was used for all statistical analysis. Methylation sites with nearby SNPs (as defined by Illumina, dbSNP137, version 2) with a minor allele frequency greater than 0.05 in any population were not included in our results.