UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity

Wahl, S; Drong, A; Lehne, B; Loh, M; Scott, WR; Kunze, S; Tsai, PC; ... Chambers, JC; + view all (2017) Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature , 541 (7635) pp. 81-86. 10.1038/nature20784. Green open access

[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Main.pdf - ["content_typename_Accepted version" not defined]

Download (506kB) | Preview
[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Supplementary Information.pdf - ["content_typename_Accepted version" not defined]

Download (1MB) | Preview
[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Extended data.pdf - ["content_typename_Accepted version" not defined]

Download (1MB) | Preview
[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Figure 1.pdf - ["content_typename_Accepted version" not defined]

Download (701kB) | Preview
[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Figure 2.pdf - ["content_typename_Accepted version" not defined]

Download (225kB) | Preview
[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Figure 3.pdf - ["content_typename_Accepted version" not defined]

Download (108kB) | Preview
[img]
Preview
Text
Batterham_Nature 2015-03-03573D - Figure 4.pdf - ["content_typename_Accepted version" not defined]

Download (109kB) | Preview

Abstract

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. 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 with P < 1 × 10(-7), range P = 9.2 × 10(-8) to 6.0 × 10(-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 that 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 < 9.0 × 10(-6), range P = 5.5 × 10(-6) to 6.1 × 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10(-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.

Type: Article
Title: Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nature20784
Publisher version: http://doi.org/10.1038/nature20784
Language: English
Additional information: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Keywords: Epigenomics; Obesity
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Metabolism and Experi Therapeutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: http://discovery.ucl.ac.uk/id/eprint/1534933
Downloads since deposit
56Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item