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Series GSE61151 Query DataSets for GSE61151
Status Public on Nov 12, 2014
Title Temporal stability and determinants of white blood cell DNA methylation in the Breakthrough Generations Study
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Background: Epigenome-wide association studies (EWAS) using measurements of blood DNA methylation are performed to identify associations of methylation changes with environmental and lifestyle exposures, and with risk of developing disease. However, little is known about the variation of methylation markers in the population and their stability over time, both important factors in the design and interpretation of EWAS.
Methods: We estimated the intraclass correlation coefficient (ICC) for each probe on the Illumina 450K methylation array in paired samples collected approximately six years apart from 92 participants in the Breakthrough Generations Study. We also evaluated relationships with age, reproductive and hormonal history, weight, alcohol intake and smoking.
Results: Approximately 17% of probes on the 450K array had an ICC>0.50 and were considered stable variable methylated probes (stable-VMPs). Stable-VMPs were enriched for probes located in "shores" bordering CpG islands, and at approximately 1.3kb downstream from the transcription start site in the transition between the unmethylated promoter and methylated gene body. Both cross-sectional and longitudinal data analyses provided strong evidence for associations between changes in methylation levels and ageing. Smoking-related probes at 2q37.1 and AHRR were stable-VMPs and, as previously reported, related to time since quitting smoking. We also observed an excess of associations between methylation and weight changes beyond those expected by chance.
Conclusion: Our results provide support for the use of WBC DNA methylation as a biomarker of exposure in EWAS. Larger studies, preferably with repeated measures over time, will be required to establish associations between specific probes and exposures.
Overall design The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across 485,577 CpGs . Samples included each sample taken at baseline and a second blood sample taken on average 6 years later, we include 4 pairs of duplicate samples and in vitro methylated (100%) and unmethylated (0%) control DNA samples.
Bisulphite converted DNA was hybridized to the Illumina Infinium 450k Human Methylation Beadchip
Contributor(s) Flanagan JM, Garcia-Closas M
Citation(s) 25371448
Submission date Sep 05, 2014
Last update date Mar 22, 2019
Contact name James M Flanagan
Organization name Imperial College London
Department Surgery and Cancer
Lab Epigenetics Unit
Street address Hammersmith Hospital, Du Cane Rd
City London
State/province London
ZIP/Postal code W12 0NN
Country United Kingdom
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (188)
GSM1498474 genomic DNA peripheral blood DNA p1A1
GSM1498475 genomic DNA peripheral blood DNA p1B1
GSM1498476 genomic DNA peripheral blood DNA p1C1
BioProject PRJNA260356

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE61151_Matrix_raw_signal.txt.gz 799.5 Mb (ftp)(http) TXT
GSE61151_RAW.tar 183.1 Mb (http)(custom) TAR
GSE61151_Summary_icc_M.txt.gz 15.1 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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