Methylomics of Gene Expression in Human Monocytes

Details

• Personal Author:
  Barr RG ; Burke GL ; Cui W ; De La Fuente A ; Ding J ; Hawkins GA ; Herrington DM ; Hoeschele I ; Howard TD ; Jacobs DR Jr. ; Kaufman JD ; Liu Y ; Lohman K ; Mccall CE ; Morris J ; Post W ; Register TC ; Reynolds LM ; Shea S ; Siscovick D ; Smith SG ; Tracy RP
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Genetics Occupational Health Safety
• Keywords:
  Cohort Studies Deoxyribonucleic Acids DNA Gene Expression Genes Genetic Factors Genomics Health Effects
• ISSN:
  0964-6906
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Minnesota ; New York ; North Carolina ; OSHA Region 1 ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; Vermont ; Virginia ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  22
• Issue:
  24
• NIOSHTIC Number:
  nn:20055111
• Citation:
  Hum Mol Genet 2013 Dec; 22(24):5065-5074
• Contact Point Address:
  Yongmei Liu, Division of Public Health Sciences, Department of Epidemiology and Prevention,Wake Forest School of Medicine, Winston-Salem NC 27157, USA
• Email:
  yoliu@wakehealth.edu
• Federal Fiscal Year:
  2014
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Human Molecular Genetics
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:47a1f11183e4798ff94054aa5a305bfba13026d98caf17599ebad52b09181103bf2dc9bc969ae779e46591ce71935a91a7d767e89d3d1baf2acf73b8f8e0366f
• Download URL:
  https://stacks.cdc.gov/view/cdc/217480/cdc_217480_DS1.pdf
• File Type:
  [PDF - 733.89 KB ]