title: Postprandial alterations in whole-blood DNA methylation are mediated by changes in white blood cell composition.
abstract: BACKGROUND
  DNA methylation is an essential nuclear process associated with genomic functions such as transcription factor binding and the regulation of gene expression. DNA methylation patterns can also serve as potential biomarkers for disease progression and response to therapy. However, the full dynamics of DNA methylation across daily physiologic events have not been fully elucidated.
  
  
  OBJECTIVE
  We sought to study how ingesting a standardized meal acutely affects peripheral blood DNA methylation.
  
  
  METHODS
  We performed an observational study in healthy men (n = 26) on DNA methylation and gene expression in whole blood before and 160 min after the ingestion of a standardized meal. Cytosine-phosphate-guanine (CpG) methylation was assayed on the HumanMethylation450k microarray, and gene expression was measured with the Human Gene 2.1 ST Array.
  
  
  RESULTS
  Differential methylation after food intake was detected in 13% of the analyzed probes (63,207 CpG probes) at a 5% false discovery rate (FDR). This effect was driven by changes in leukocyte fractions as estimated from comparisons against methylation datasets generated from sorted leukocytes. When methylation values were adjusted for estimated leukocyte fractions, 541 probes were observed to be altered in the postprandial state (5% FDR).
  
  
  CONCLUSIONS
  Apparent alterations in DNA methylation 160 min after meal ingestion mainly reflect changes in the estimated leukocyte population in whole blood. These results have major methodologic implications for genome-wide methylation studies because they highlight the strong underlying effects of changes in leukocyte fractions on CpG methylation patterns as well as the potential importance of meal-standardized sampling procedures for future investigations when alterations in white blood cell fractions are unavailable. This trial was registered at clinicaltrials.gov as LSF008786.
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden; mathias.rask-andersen@neuro.uu.se.
authors.forename: Mathias
authors.identifier: http://orcid.org/0000-0002-8008-4659
authors.initials: M
authors.lastname: Rask-Andersen
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bringeland
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Emil K
authors.initials: EK
authors.lastname: Nilsson
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Marcus
authors.initials: M
authors.lastname: Bandstein
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Marcela
authors.initials: M
authors.lastname: Olaya Búcaro
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition, Nuthetal, Germany; and German Center of Diabetes Research, Neuherberg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Department of Experimental Diabetology, German Institute of Human Nutrition, Nuthetal, Germany; and German Center of Diabetes Research, Neuherberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schürmann
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Pleunie S
authors.initials: PS
authors.lastname: Hogenkamp
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Department of Neuroscience, Division of Functional Pharmacology, Biomedical Center, Uppsala University, Uppsala, Sweden;
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
mesh_terms: D000328:Adult; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007962:Leukocytes; D008297:Male; D062407:Meals / Q000502:physiology*; D019518:Postprandial Period; D055815:Young Adult
keywords: DNA methylation; EWAS; HumanMethylation450k; food intake; ghrelin