Research output

Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals

Research output: Contribution to journalArticleAcademicpeer-review

Associated researcher

  • BIOS Consortium, CHARGE Consortium Epigenetics Working Group, CHARGE Consortium Nutrition Working Group

Associated organisations

Abstract

BACKGROUND: Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans.

OBJECTIVE: The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes.

METHODS: A large-scale epigenome-wide association study of folate and vitamin B-12 intake was performed on DNA from 5841 participants from 10 cohorts using Illumina 450k arrays. Folate and vitamin B-12 intakes were calculated from food-frequency questionnaires (FFQs). Continuous and categorical (low compared with high intake) linear regression mixed models were applied per cohort, controlling for confounders. A meta-analysis was performed to identify significant differentially methylated positions (DMPs) and regions (DMRs), and a pathway analysis was performed on the DMR annotated genes.

RESULTS: The categorical model resulted in 6 DMPs, which are all negatively associated with folate intake, annotated to FAM64A, WRAP73, FRMD8, CUX1, and LCN8 genes, which have a role in cellular processes including centrosome localization, cell proliferation, and tumorigenesis. Regional analysis showed 74 folate-associated DMRs, of which 73 were negatively associated with folate intake. The most significant folate-associated DMR was a 400-base pair (bp) spanning region annotated to the LGALS3BP gene. In the categorical model, vitamin B-12 intake was associated with 29 DMRs annotated to 48 genes, of which the most significant was a 1100-bp spanning region annotated to the calcium-binding tyrosine phosphorylation-regulated gene (CABYR). Vitamin B-12 intake was not associated with DMPs.

CONCLUSIONS: We identified novel epigenetic loci that are associated with folate and vitamin B-12 intake. Interestingly, we found a negative association between folate and DNA methylation. Replication of these methylation loci is necessary in future studies.

    Research areas

  • ARRAY, CALM, CANCER, DNA methylation, Epigenome-wide Association Study, FFQ, GLOBAL METHYLATION, INTERACTOR CATS, ONE-CARBON METABOLISM, PREVALENCE, PROTEIN, RISK-FACTORS, SURVIVAL, diet, epigenetics, folate, genome-wide, vitamin B-12
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Details

Original languageEnglish
Article number15
Pages (from-to)437-450
Number of pages14
JournalAmerican Journal of Clinical Nutrition
Volume110
Issue number2
Early online date5 Jun 2019
DOIs
Publication statusPublished - Aug 2019