Methylomics of gene expression in human monocytes

Yongmei Liu, Jingzhong Ding, Lindsay M. Reynolds, Kurt Lohman, Thomas C. Register, Alberto De la Fuente, Timothy D. Howard, Greg A. Hawkins, Wei Cui, Jessica Morris, Shelly G. Smith, R. Graham Barr, Joel D. Kaufman, Gregory L. Burke, Wendy Post, Steven Shea, Charles E. Mccall, David Siscovick, David R. Jacobs, Russell P. TracyDavid M. Herrington, Ina Hoeschele

Research output: Contribution to journalArticle

Abstract

DNA methylation is one of several epigenetic mechanisms that contribute to the regulation of gene expression; however, the extent to which methylation of CpG dinucleotides correlates with gene expression at the genome-wide level is still largely unknown. Using purified primary monocytes from subjects in a large community-based cohort (n = 1264), we characterized methylation (>485 000 CpG sites) and mRNA expression (>48K transcripts) and carried out genome-wide association analyses of 8370 expression phenotypes. We identified 11 203 potential cis-acting CpG loci whose degree of methylation was associated with gene expression (eMS) at a false discovery rate threshold of 0.001. Most of the associations were consistent in effect size and direction of effect across sex and three ethnicities. Contrary to expectation, these eMS were not predominately enriched in promoter regions, or CpG islands, but rather in the 3' UTR, gene bodies, CpG shores or 'offshore' sites, and both positive and negative correlations between methylation and expression were observed across all locations. eMS were enriched for regions predicted to be regulatory by ENCODE (Encyclopedia of DNA Elements) data in multiple cell types, particularly enhancers. One of the strongest association signals detected (P < 2.2 × 10-308) was a methylation probe (cg17005068) in the promoter/enhancer region of the glutathione S-transferase theta 1 gene (GSTT1, encoding the detoxification enzyme) with GSTT1 mRNA expression. Our study provides a detailed description of the epigenetic architecture in human monocytes and its relationship to gene expression. These data may help prioritize interrogation of biologically relevant methylation loci and provide new insights into the epigenetic basis of human health and diseases.

Original languageEnglish (US)
Article numberddt356
Pages (from-to)5065-5074
Number of pages10
JournalHuman molecular genetics
Volume22
Issue number24
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Methylomics of gene expression in human monocytes'. Together they form a unique fingerprint.

  • Cite this

    Liu, Y., Ding, J., Reynolds, L. M., Lohman, K., Register, T. C., De la Fuente, A., Howard, T. D., Hawkins, G. A., Cui, W., Morris, J., Smith, S. G., Barr, R. G., Kaufman, J. D., Burke, G. L., Post, W., Shea, S., Mccall, C. E., Siscovick, D., Jacobs, D. R., ... Hoeschele, I. (2013). Methylomics of gene expression in human monocytes. Human molecular genetics, 22(24), 5065-5074. [ddt356]. https://doi.org/10.1093/hmg/ddt356