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The first epigenome-wide association study of BMI identified DNA methylation at an HIF3A locus associated with BMI. We tested the hypothesis that DNA methylation variants are associated with BMI according to intake of B vitamins. In two large cohorts, we found significant interactions between the DNA methylation-associated HIF3A single nucleotide polymorphism (SNP) rs3826795 and intake of B vitamins on 10-year changes in BMI. The association between rs3826795 and BMI changes consistently increased across the tertiles of total vitamin B2 and B12 intake (all P for interaction <0.01). The differences in the BMI changes per increment of minor allele were -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B2 intake and -0.10 (SE 0.06), -0.01 (SE 0.06), and 0.10 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B12 intake. In two independent cohorts, a DNA methylation variant in HIF3A was associated with BMI changes through interactions with total or supplemental vitamin B2, vitamin B12, and folate. These findings suggest a potential causal relation between DNA methylation and adiposity.

Original publication

DOI

10.2337/db15-0264

Type

Journal article

Journal

Diabetes

Publication Date

09/2015

Volume

64

Pages

3146 - 3154

Keywords

Adult, Aged, Basic Helix-Loop-Helix Transcription Factors, Body Mass Index, Cohort Studies, DNA Methylation, Diet, Female, Folic Acid, Gene-Environment Interaction, Humans, Longitudinal Studies, Male, Middle Aged, Obesity, Overweight, Polymorphism, Single Nucleotide, Prospective Studies, Riboflavin, United Kingdom, United States, Vitamin B 12, Vitamin B 6, Vitamin B Complex, Weight Gain