An empirically driven data reduction method on the human 450K methylation array to remove tissue specific non-variable CpGs.
Population based epigenetic association studies of disease and exposures are becoming more common with the availability of economical genome-wide technologies for interrogation of the methylome, such as the Illumina 450K Human Methylation Array (450K). Often, the expected small number of differentially methylated cytosine-guanine pairs (CpGs) in studies of the human methylome presents a statistical challenge, as the large number of CpGs measured on the 450K necessitates careful multiple test correction. While the 450K is a highly useful tool for population epigenetic studies, many of the CpGs tested are not variable and thus of limited information content in the context of the study and tissue. CpGs with observed lack of variability in the tissue under study could be removed to reduce the data dimensionality, limit the severity of multiple test correction and allow for improved detection of differential DNA methylation.



Here, we performed a meta-analysis of 450K data from three commonly studied human tissues, namely blood (605 samples), buccal epithelial cells (121 samples) and placenta (157 samples). We developed lists of CpGs that are non-variable in each tissue.



These lists are surprisingly large (blood 114,204 CpGs, buccal epithelial cells 120,009 CpGs and placenta 101,367 CpGs) and thus will be valuable filters for epigenetic association studies, considerably reducing the dimensionality of the 450K and subsequently the multiple testing correction severity.



We propose this empirically derived method for data reduction to allow for more power in detecting differential DNA methylation associated with exposures in studies on the human methylome.
Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
Rachel D
RD
Edgar
Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
Meaghan J
MJ
Jones
Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
Wendy P
WP
Robinson
Department of Medical Genetics, BC Children's Hospital, University of British Columbia, Vancouver, Canada.
Michael S
MS
Kobor
D001774:Blood Chemical Analysis; D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D009055:Mouth / Q000737:chemistry*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D012984:Software
450K; DNA methylation; Dimensionality reduction; Filter; Multiple-test correction; Non-variable; Power; Tissue