Epigenetics meets metabolomics

An epigenome-wide association study with blood serum metabolic traits

Ann Kristin Petersen, Sonja Zeilinger, Gabi Kastenmüller, Römisch Margl Werner, Markus Brugger, Annette Peters, Christine Meisinger, Konstantin Strauch, Christian Hengstenberg, Philipp Pagel, Fritz Huber, Robert P. Mohney, Harald Grallert, Thomas Illig, Jerzy Adamski, Melanie Waldenberger, Christian Gieger, Karsten Suhre

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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. Totest 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 Human Methylation 450 Bead Chip 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 atgenome-wide significance that have a genetic variant as confounder (P = 3.9 × 10-20 to 2.0 × 10-108, r2 = 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 × 10-14 to 2.7 × 10-27, r2 = 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.

Original languageEnglish
Pages (from-to)534-545
Number of pages12
JournalHuman Molecular Genetics
Volume23
Issue number2
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Metabolomics
Epigenomics
DNA Methylation
Methylation
Serum
Population
Sulfates
Life Style
Smoking
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Petersen, A. K., Zeilinger, S., Kastenmüller, G., Werner, R. M., Brugger, M., Peters, A., ... Suhre, K. (2014). Epigenetics meets metabolomics: An epigenome-wide association study with blood serum metabolic traits. Human Molecular Genetics, 23(2), 534-545. https://doi.org/10.1093/hmg/ddt430

Epigenetics meets metabolomics : An epigenome-wide association study with blood serum metabolic traits. / Petersen, Ann Kristin; Zeilinger, Sonja; Kastenmüller, Gabi; Werner, Römisch Margl; Brugger, Markus; Peters, Annette; Meisinger, Christine; Strauch, Konstantin; Hengstenberg, Christian; Pagel, Philipp; Huber, Fritz; Mohney, Robert P.; Grallert, Harald; Illig, Thomas; Adamski, Jerzy; Waldenberger, Melanie; Gieger, Christian; Suhre, Karsten.

In: Human Molecular Genetics, Vol. 23, No. 2, 2014, p. 534-545.

Research output: Contribution to journalArticle

Petersen, AK, Zeilinger, S, Kastenmüller, G, Werner, RM, Brugger, M, Peters, A, Meisinger, C, Strauch, K, Hengstenberg, C, Pagel, P, Huber, F, Mohney, RP, Grallert, H, Illig, T, Adamski, J, Waldenberger, M, Gieger, C & Suhre, K 2014, 'Epigenetics meets metabolomics: An epigenome-wide association study with blood serum metabolic traits', Human Molecular Genetics, vol. 23, no. 2, pp. 534-545. https://doi.org/10.1093/hmg/ddt430
Petersen, Ann Kristin ; Zeilinger, Sonja ; Kastenmüller, Gabi ; Werner, Römisch Margl ; Brugger, Markus ; Peters, Annette ; Meisinger, Christine ; Strauch, Konstantin ; Hengstenberg, Christian ; Pagel, Philipp ; Huber, Fritz ; Mohney, Robert P. ; Grallert, Harald ; Illig, Thomas ; Adamski, Jerzy ; Waldenberger, Melanie ; Gieger, Christian ; Suhre, Karsten. / Epigenetics meets metabolomics : An epigenome-wide association study with blood serum metabolic traits. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 2. pp. 534-545.
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