Participants had a whole blood sample drawn at study entry. The DNeasy Blood and Tissue Kit (Qiagen, Hilden, Germany) was used to extract DNA from this sample. Unmethylated cytosine residues present in the DNA extract were converted to uracil using the EZ DNA Methylation Kit (Zymo, Irvine, California, USA). DNA methylation profiles were obtained using the Illumina Infinium MethylationEPIC BeadChip microarray which interrogates 863 904 CpG sites and covers 95% of all genes and 95% of CpG islands.16 (link) The ratio of the methylated probe intensity to the overall intensity (β value) was calculated for each CpG and ranged from 0 (all unmethylated) to 1 (all methylated) and then transformed to M-values (log2 ratio of the intensity of the methylated probe to unmethylated CpG probe). CpG probes were filtered based on the detection quality and probes with a detection p>1e−10 were excluded from downstream analyses. In addition, non-CpG, XY-linked, single nucleotide polymorphism (SNP) and cross-hybridisation probes were also removed (839 418 CpGs were retained). Lastly, background correction, normalisation and batch correction were performed using the normal–exponential out-of-band,17 (link) mixture quantile normalisation18 (link) and ComBat19 (link) methods, respectively.