DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework
| Autor: | Abigail Fraser, Oliver Lyttleton, Debbie A Lawlor, George Davey Smith, Susan M. Ring, Gemma C Sharp, Rebecca C Richmond, Caroline L Relton, Tom R. Gaunt, Wendy L. McArdle, Mary E. Ward |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Longitudinal study Adolescent Endocrinology Diabetes and Metabolism Mothers Biology Body Mass Index Cohort Studies 03 medical and health sciences Child Development Thinness Basic Helix-Loop-Helix Transcription Factors Internal Medicine Birth Weight Humans Longitudinal Studies Prospective Studies Child Adiposity Genetics Confounding Infant Newborn Confounding Factors Epidemiologic Mendelian Randomization Analysis Methylation Adolescent Development DNA Methylation Overweight Causality Repressor Proteins HIF3A Cross-Sectional Studies 030104 developmental biology England CpG site DNA methylation Female Apoptosis Regulatory Proteins Body mass index Obesity Studies |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db15-0996 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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