Projects per year
Abstract
Overweight and obesity affect ~1.5 billion people worldwide, and are major risk factors for type-2 diabetes (T2D), cardiovascular disease and related metabolic and inflammatory disturbances.1,2 Although the mechanisms linking adiposity to its clinical sequelae are poorly understood, recent studies suggest that adiposity may influence DNA methylation,3-6 a key regulator of gene expression and molecular phenotype.7 Here we use epigenome-wide association to show that body mass index (BMI, a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci at P<1x10-7, range P=9.2x10-8 to 6.0x10-46; N=10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find the methylation loci are enriched for functional genomic features in multiple tissues (P<0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P<9.0x10-6, range P=5.5x10-6 to 6.1x10-35, N=1,785 samples). The methylation loci identified highlight genes involved in lipid and lipoprotein metabolism, substrate transport, and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future type-2 diabetes (relative risk per 1SD increase in Methylation Risk Score: 2.3 [2.07-2.56]; P=1.1x10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type-2 diabetes and other adverse clinical consequences of obesity.
Original language | English |
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Pages (from-to) | 81-86 |
Number of pages | 6 |
Journal | Nature |
Volume | 541 |
Issue number | 7635 |
Early online date | 21 Dec 2016 |
DOIs | |
Publication status | Published - 5 Jan 2017 |
Keywords
- Epigenomics
- Obesity
Fingerprint
Dive into the research topics of 'Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity'. Together they form a unique fingerprint.Projects
- 3 Finished
Profiles
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Professor Caroline L Relton
- Bristol Medical School (PHS) - Professor of Epigenetic Epidemiology and MRC Investigator
- Bristol Population Health Science Institute
- MRC Integrative Epidemiology Unit
- Cancer
Person: Academic , Member, Group lead
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Dr Rebecca Richmond
- Bristol Medical School (PHS) - Senior Research Fellow
- Bristol Population Health Science Institute
- Bristol Neuroscience
Person: Academic , Member