TY - JOUR
T1 - Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome
AU - Costeira, Ricardo
AU - Evangelista, Laila
AU - Wilson, Rory
AU - Yan, Xinyu
AU - Hellbach, Fabian
AU - Sinke, Lucy
AU - Christiansen, Colette
AU - Villicaña, Sergio
AU - Masachs, Olatz M.
AU - Tsai, Pei Chien
AU - Mangino, Massimo
AU - Menni, Cristina
AU - Berry, Sarah E.
AU - Beekman, Marian
AU - van Heemst, Diana
AU - Slagboom, P. Eline
AU - Heijmans, Bastiaan T.
AU - Suhre, Karsten
AU - Kastenmüller, Gabi
AU - Gieger, Christian
AU - Peters, Annette
AU - Small, Kerrin S.
AU - Linseisen, Jakob
AU - Waldenberger, Melanie
AU - Bell, Jordana T.
N1 - Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - B vitamins
KW - Biomarkers
KW - DNA methylation
KW - Diet
KW - Folate
KW - Metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85174493052&partnerID=8YFLogxK
U2 - 10.1186/s13148-023-01578-7
DO - 10.1186/s13148-023-01578-7
M3 - 文章
C2 - 37858220
AN - SCOPUS:85174493052
SN - 1868-7075
VL - 15
JO - Clinical Epigenetics
JF - Clinical Epigenetics
IS - 1
M1 - 166
ER -