PMID- 24014485
OWN - NLM
STAT- MEDLINE
DCOM- 20140805
LR  - 20211021
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 23
IP  - 2
DP  - 2014 Jan 15
TI  - Epigenetics meets metabolomics: an epigenome-wide association study with blood 
      serum metabolic traits.
PG  - 534-45
LID - 10.1093/hmg/ddt430 [doi]
AB  - Previously, we reported strong influences of genetic variants on metabolic 
      phenotypes, some of them with clinical relevance. Here, we hypothesize that DNA 
      methylation may have an important and potentially independent effect on human 
      metabolism. To test this hypothesis, we conducted what is to the best of our 
      knowledge the first epigenome-wide association study (EWAS) between DNA 
      methylation and metabolic traits (metabotypes) in human blood. We assess 649 
      blood metabolic traits from 1814 participants of the Kooperative 
      Gesundheitsforschung in der Region Augsburg (KORA) population study for 
      association with methylation of 457 004 CpG sites, determined on the Infinium 
      HumanMethylation450 BeadChip platform. Using the EWAS approach, we identified two 
      types of methylome-metabotype associations. One type is driven by an underlying 
      genetic effect; the other type is independent of genetic variation and 
      potentially driven by common environmental and life-style-dependent factors. We 
      report eight CpG loci at genome-wide significance that have a genetic variant as 
      confounder (P = 3.9 x 10(-20) to 2.0 x 10(-108), r(2) = 0.036 to 0.221). Seven 
      loci display CpG site-specific associations to metabotypes, but do not exhibit 
      any underlying genetic signals (P = 9.2 x 10(-14) to 2.7 x 10(-27), r(2) = 0.008 
      to 0.107). We further identify several groups of CpG loci that associate with a 
      same metabotype, such as 4-vinylphenol sulfate and 
      4-androsten-3-beta,17-beta-diol disulfate. In these cases, the association 
      between CpG-methylation and metabotype is likely the result of a common external 
      environmental factor, including smoking. Our study shows that analysis of EWAS 
      with large numbers of metabolic traits in large population cohorts are, in 
      principle, feasible. Taken together, our data suggest that DNA methylation plays 
      an important role in regulating human metabolism.
FAU - Petersen, Ann-Kristin
AU  - Petersen AK
AD  - Institute of Genetic Epidemiology.
FAU - Zeilinger, Sonja
AU  - Zeilinger S
FAU - Kastenmuller, Gabi
AU  - Kastenmuller G
FAU - Romisch-Margl, Werner
AU  - Romisch-Margl W
FAU - Brugger, Markus
AU  - Brugger M
FAU - Peters, Annette
AU  - Peters A
FAU - Meisinger, Christine
AU  - Meisinger C
FAU - Strauch, Konstantin
AU  - Strauch K
FAU - Hengstenberg, Christian
AU  - Hengstenberg C
FAU - Pagel, Philipp
AU  - Pagel P
FAU - Huber, Fritz
AU  - Huber F
FAU - Mohney, Robert P
AU  - Mohney RP
FAU - Grallert, Harald
AU  - Grallert H
FAU - Illig, Thomas
AU  - Illig T
FAU - Adamski, Jerzy
AU  - Adamski J
FAU - Waldenberger, Melanie
AU  - Waldenberger M
FAU - Gieger, Christian
AU  - Gieger C
FAU - Suhre, Karsten
AU  - Suhre K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130906
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
SB  - IM
MH  - Adult
MH  - Aged
MH  - Blood/*metabolism
MH  - CpG Islands
MH  - *DNA Methylation
MH  - *Epigenesis, Genetic
MH  - Female
MH  - Gene Expression Regulation
MH  - Gene-Environment Interaction
MH  - Genetic Variation
MH  - Genome, Human
MH  - *Genome-Wide Association Study
MH  - Humans
MH  - Male
MH  - *Metabolome
MH  - Metabolomics
MH  - Middle Aged
MH  - Quantitative Trait Loci
MH  - Smoking/genetics
PMC - PMC3869358
EDAT- 2013/09/10 06:00
MHDA- 2014/08/06 06:00
PMCR- 2013/09/06
CRDT- 2013/09/10 06:00
PHST- 2013/09/10 06:00 [entrez]
PHST- 2013/09/10 06:00 [pubmed]
PHST- 2014/08/06 06:00 [medline]
PHST- 2013/09/06 00:00 [pmc-release]
AID - ddt430 [pii]
AID - 10.1093/hmg/ddt430 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2014 Jan 15;23(2):534-45. doi: 10.1093/hmg/ddt430. Epub 2013 Sep 
      6.