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

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 24; no. 3; pp. 490 - 497
• Main Authors: Shvetsov, Yurii B., Song, Min-Ae, Cai, Qiuyin, Tiirikainen, Maarit, Xiang, Yong-Bing, Shu, Xiao-Ou, Yu, Herbert
• Format: Journal Article
• Language: English
• Published: United States 01.03.2015
• Subjects: Adult; Aged; Blood Chemical Analysis - methods; Cohort Studies; CpG Islands; DNA - blood; DNA - genetics; DNA Methylation; Epigenomics; Female; Genome, Human; Humans; Middle Aged; Prospective Studies
• ISSN: 1055-9965; 1538-7755; 1538-7755
• 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.