title: Epigenome-wide search for association of serum 25-hydroxyvitamin D concentration with leukocyte DNA methylation in a large cohort of older men.
abstract: OBJECTIVE
  We aimed for an epigenome-wide identification of vitamin D-associated CpG sites in leukocyte DNA.
  
  
  METHODS
  Infinium HumanMethylation450BeadChip measurements in 402 Caucasian older men were evaluated for significant association with 25-hydroxy-vitamin (25(OH)D) using Spearman's correlation and median regression to adjust for confounding variables. A cross-validation approach as well as a bootstrapping procedure were implemented to determine the replicability of significant associations. Multiple testing was corrected for by Benjamini-Hochberg or Bonferroni.
  
  
  RESULTS
  Although in the screening subcohorts significant associations of DNAm with 25(OH)D were observed in the validation cohorts these associations were not replicated after adjustment for potential confounders. At none of the 361,945 CpGs a significant association of DNAm with 25(OH)D was found in all 100 random bootstrap samples, but in comparison at 462 CpGs for the well-established association with age.
  
  
  CONCLUSIONS
  Leukocyte DNAm was not associated with 25(OH)D levels after validation and consideration of confounders.
authors.affiliation: Division of Clinical Epidemiology & Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Im Neuenheimer Feld 280, Germany.|School of Public Health, Curtin University Perth, 6102 Bentley, Kent Street, Australia.
authors.forename: Ines
authors.initials: I
authors.lastname: Florath
authors.affiliation: Division of Clinical Epidemiology & Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Im Neuenheimer Feld 280, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Schöttker
authors.affiliation: Division of Clinical Epidemiology & Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Im Neuenheimer Feld 280, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Butterbach
authors.affiliation: Core Facility Genomics & Proteomics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Im Neuenheimer Feld 280, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bewerunge-Hudler
authors.affiliation: Division of Clinical Epidemiology & Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Im Neuenheimer Feld 280, Germany.|Division of Clinical Epidemiology & Aging Research, Division of Preventive Oncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Im Neuenheimer Feld 280, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
mesh_terms: D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D005858:Germany; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D044465:White People
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25(OH)D; DNA methylation; bootstrapping; cohort study; cross-validation; elderly; epigenetics; humans; vitamin D