title: DNA Methylation Variants at HIF3A Locus, B-Vitamin Intake, and Long-term Weight Change: Gene-Diet Interactions in Two U.S. Cohorts.
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 -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.
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases and Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Sylvia H
authors.initials: SH
authors.lastname: Ley
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA.
authors.forename: Janey
authors.initials: J
authors.lastname: Wiggs
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA.
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Boston, MA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA nhlqi@channing.harvard.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015992:Body Mass Index; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D004032:Diet / Q000706:statistics & numerical data*; D005260:Female; D005492:Folic Acid; D059647:Gene-Environment Interaction; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D050177:Overweight / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012097:Repressor Proteins; D012256:Riboflavin; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D014805:Vitamin B 12; D025101:Vitamin B 6; D014803:Vitamin B Complex; D015430:Weight Gain / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D005492:Folic Acid; D012097:Repressor Proteins; D012256:Riboflavin; D014805:Vitamin B 12; D025101:Vitamin B 6; D014803:Vitamin B Complex; C116973:HIF3A protein, human