Intraindividual variation and short-term temporal trend in DNA methylation of human blood.

Shvetsov YB, Song MA, Cai Q, Tiirikainen M, Xiang YB, Shu XO, Yu H
Cancer Epidemiol Biomarkers Prev. 2015 24 (3): 490-7

PMID: 25538225 · PMCID: PMC4355238 · DOI:10.1158/1055-9965.EPI-14-0853

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 low-variability 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. Cancer Epidemiol Biomarkers Prev; 24(3); 490-7. ©2014 AACR.

©2014 American Association for Cancer Research.

MeSH Terms (13)

Adult Aged Blood Chemical Analysis Cohort Studies CpG Islands DNA DNA Methylation Epigenomics Female Genome, Human Humans Middle Aged Prospective Studies

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