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DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework.
- Source :
-
Diabetes [Diabetes] 2016 May; Vol. 65 (5), pp. 1231-44. Date of Electronic Publication: 2016 Feb 09. - Publication Year :
- 2016
-
Abstract
- Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation.<br /> (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
- Subjects :
- Adolescent
Adult
Apoptosis Regulatory Proteins
Basic Helix-Loop-Helix Transcription Factors metabolism
Birth Weight
Causality
Child
Cohort Studies
Confounding Factors, Epidemiologic
Cross-Sectional Studies
England epidemiology
Female
Humans
Infant, Newborn
Longitudinal Studies
Male
Mothers
Overweight epidemiology
Overweight etiology
Overweight genetics
Overweight metabolism
Prospective Studies
Repressor Proteins
Thinness epidemiology
Thinness etiology
Thinness genetics
Thinness metabolism
Adiposity
Adolescent Development
Basic Helix-Loop-Helix Transcription Factors genetics
Body Mass Index
Child Development
DNA Methylation
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 65
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 26861784
- Full Text :
- https://doi.org/10.2337/db15-0996