Intraindividual Variation and Short-term Temporal Trend in DNA Methylation of Human Blood

Background: Between-and within-person variation in DNA methylation levels are important parameters to be considered in epigenome-wide association studies. Temporal change is one source of within-person variation in DNA methylation that has been linked to aging and disease. Methods: We analyzed CpG-site-specific intraindividual variation and short-term temporal trend in leukocyte DNA methylation among 24 healthy Chinese women, with blood samples drawn at study entry and after 9 months. Illumina HumanMethylation450 BeadChip was used to measure methylation. Intraclass correlation coefficients (ICC) and trend estimates were summarized by genomic location and probe type. Results: The median ICC was 0.36 across nonsex chromosomes and 0.80 on the X chromosome. There was little difference in ICC profiles by genomic region and probe type. Among CpG loci with high variability between participants, more than 99% had ICC > 0.8. Statistically significant trend was observed in 10.9% CpG loci before adjustment for cell-type composition and in 3.4% loci after adjustment. Conclusions: For CpG loci differentially methylated across subjects, methylation levels can be reliably assessed with one blood sample. More samples per subject are needed for lowvariability and unmethylated loci. Temporal changes are largely driven by changes in cell-type composition of blood samples, but temporal trend unrelated to cell types is detected in a small percentage of CpG sites. Impact: This study shows that one measurement can reliably assess methylation of differentially methylated CpG loci. (c) 2014 AACR.