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Lookup NU author(s): Professor Caroline Relton
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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 approximate to 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.
Author(s): Richmond RC, Sharp GC, Ward ME, Fraser A, Lyttleton O, McArdle WL, Ring SM, Gaunt TR, Lawlor DA, Smith GD, Relton CL
Publication type: Article
Publication status: Published
Journal: Diabetes
Year: 2016
Volume: 65
Issue: 5
Pages: 1231-1244
Print publication date: 01/05/2016
Online publication date: 21/04/2016
Acceptance date: 01/02/2016
ISSN (print): 0012-1797
ISSN (electronic): 1939-327X
Publisher: American Diabetes Association
URL: http://dx.doi.org/10.2337/db15-0996
DOI: 10.2337/db15-0996
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