DNA methylation variants at HIF3A locus, B-vitamin intake, and long-term weight change: Gene-diet interactions in two U.S. Cohorts

Tao Huang, Yan Zheng, Qibin Qi, Min Xu, Sylvia H. Ley, Yanping Li, Jae H. Kang, Janey Wiggs, Louis R. Pasquale, Andrew T. Chan, Eric B. Rimm, David J. Hunter, Joann E. Manson, Walter C. Willett, Frank B. Hu, Lu Qi

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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 20.10 (SE 0.06), 20.01 (SE 0.06), and 0.12 (SE 0.07) within subgroups defined by increasing tertiles of total vitamin B2 intake and 20.10 (SE 0.06), 20.01 (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 languageEnglish (US)
Pages (from-to)3146-3154
Number of pages9
JournalDiabetes
Volume64
Issue number9
DOIs
StatePublished - Sep 2015

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Huang, T., Zheng, Y., Qi, Q., Xu, M., Ley, S. H., Li, Y., Kang, J. H., Wiggs, J., Pasquale, L. R., Chan, A. T., Rimm, E. B., Hunter, D. J., Manson, J. E., Willett, W. C., Hu, F. B., & Qi, L. (2015). DNA methylation variants at HIF3A locus, B-vitamin intake, and long-term weight change: Gene-diet interactions in two U.S. Cohorts. Diabetes, 64(9), 3146-3154. https://doi.org/10.2337/db15-0264