Methylation profiles were measured with HumanMethylation450_15017482_v.1.1 arrays. GenomeStudio v2011.1 (Methylation Module 1.9.0; Illumina) was used to export the raw data as. idat files, which were then processed with the minfi Bioconductor package 62. Samples were normalised using the stratified quantile normalisation implemented in the ‘preprocessQuantile’ function and probes were annotated to genomic locations using the IlluminaHumanMethylation450kanno.ilmn12.hg19 Bioconductor annotation package. Subsequently, genotyping probes or probes overlapping any dbSNP or 1000 Genomes variant loci were discarded. M-values, defined as the logarithm of the fraction of the methylated and unmethylated channels M = log( Meth / Unmeth ), were used in the variance component and other downstream analysis.