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Costeira, R.* ; Evangelista, L.* ; Wilson, R. ; Yan, X.* ; Hellbach, F.* ; Sinke, L.* ; Christiansen, C.* ; Villicaña, S.* ; Masachs, O.M.* ; Tsai, P.C.* ; Mangino, M.* ; Menni, C.* ; Berry, S.E.* ; Beekman, M.* ; van Heemst, D.* ; Slagboom, P.E.* ; Heijmans, B.T.* ; Suhre, K.* ; Kastenmüller, G. ; Gieger, C. ; Peters, A. ; Small, K.S.* ; Linseisen, J.* ; Waldenberger, M. ; Bell, J.T.*

Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome.

Clin. Epigenet. 15:166 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
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BACKGROUND: B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants. RESULTS: Eighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p < 0.05), of which 7 metabolites were available in both cohorts and tested for epigenome-wide association. Three metabolites - pipecolate (metabolomic biomarker of B6 and folate intakes), pyridoxate (marker of B6 and folate) and docosahexaenoate (DHA, marker of B6) - were associated with 10, 3 and 1 differentially methylated positions (DMPs), respectively. The strongest association was observed between DHA and DMP cg03440556 in the SCD gene (effect = 0.093 ± 0.016, p = 4.07E-09). Pyridoxate, a catabolic product of vitamin B6, was inversely associated with CpG methylation near the SLC1A5 gene promoter region (cg02711608 and cg22304262) and with SLC7A11 (cg06690548), but not with corresponding changes in gene expression levels. The self-reported intake of folate and vitamin B6 had consistent but non-significant associations with the epigenetic signals. CONCLUSION: Metabolomic biomarkers are a valuable approach to investigate the effects of dietary B vitamin intake on the human epigenome.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords B Vitamins ; Biomarkers ; Dna Methylation ; Diet ; Folate ; Metabolomics; Dna Methylation; Wide Association; Pipecolic Acid; Folate; Blood; Risk; Epigenetics; Mechanisms; Nutrition; Design
ISSN (print) / ISBN 1868-7075
e-ISSN 1868-7083
Journal Clinical Epigenetics
Quellenangaben Volume: 15, Issue: 1, Pages: , Article Number: 166 Supplement: ,
Publisher Springer
Publishing Place Berlin : Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Computational Biology (ICB)
Grants Department of Health
Versus Arthritis
Wellcome Trust