Large-Scale DNA Methylation Profiling

Genome-wide DNA methylation was profiled in blood samples from 5200 individuals using the Illumina HumanMethylationEPIC BeadChips. Quality control was conducted using R [20] . ShinyMethyl [21] (link) was used to plot the log median intensity of methylated versus unmethylated signal per array with outliers being excluded upon visual inspection. The software package WateRmelon [22] was used to remove (1) samples in which ≥1% of cytosine-guanine dinucleotides had a detection P value in excess of .05; (2) probes with a beadcount of less than 3 in more than 5 samples; and (3) probes in which ≥0.5% of samples had a detection P value in excess of .05. ShinyMethyl was used to exclude samples in which predicted sex did not match recorded sex. This left a sample of 5101 available for analysis.