DNAm was measured in peripheral blood with samples collected at 10 and 18 years using either the Infinium HumanMethylation450 BeadChips or MethylationEPIC BeadChips (illumina, Inc, San Diego, CA). Preprocessing of DNAm was carried out using the CPACOR pipeline.44 (link) Details of DNAm data generation, quality control and preprocessing, as well as principal components (PC) analyses detecting latent variables for batch and technical variations, are in the Supplemental Material S1. After preprocessing, a total of 442 475 CpGs in common between the two platforms were included in the analyses.
Since blood is a mixture of functionally and developmentally distinct cell populations,45 (link) adjusting cell-type compositions was needed in analyses to reduce confounding from cell heterogeneity in DNAm measured from blood samples.46 (link) We estimated cell-type proportions using the method proposed by Jaffe and Irizarry,47 (link) adapted from Houseman et al,48 (link) using the Bioconductor minfi package.49 (link) The estimated cell-type proportions of CD4+ T cells, natural killer cells, neutrophil, B cells, monocytes and eosinophil cells were included in the analyses as confounding factors.