Format

Send to

Choose Destination
Int J Obes (Lond). 2018 Dec;42(12):2022-2035. doi: 10.1038/s41366-018-0064-7. Epub 2018 May 1.

Epigenome-wide association study of adiposity and future risk of obesity-related diseases.

Author information

1
Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
2
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France.
3
Italian Institute for Genomic Medicine (IIGM), Turin, Italy.
4
Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan, Italy.
5
Istituto per lo Studio e la Prevenzione Oncologica (ISPO Toscana), Florence, Italy.
6
Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
7
Piedmont Reference Centre for Epidemiology and Cancer Prevention (CPO Piemonte), Turin, Italy.
8
Cancer Registry and Histopathology Unit, Azienda Ospedaliera "Civile-M.P. Arezzo", Ragusa, Italy.
9
Department of Medical Sciences, University of Turin, Turin, Italy.
10
Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli (IS), Italy.
11
Department of Biobank Research, Umeå University, Umeå, Sweden.
12
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
13
Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
14
Institute of Biology, Medicinal Chemistry, and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
15
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
16
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
17
Department of Social and Preventive Medicine, University of Malaya, Kuala Lumpur, Malaysia.
18
Centre for Biological Sciences, University of Southampton, Southampton, UK.
19
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
20
MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
21
Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
22
Department of Community Medicine, University of Tromsø (UiT)-The Artic University of Norway, Tromsø, Norway.
23
Department of Medical Sciences, Unit of Cancer Epidemiology-CERMS, University of Turin, Turin, Italy.
24
CNRS UMR8199, Pasteur Institute of Lille, Lille University, Lille, France.
25
Department of Genomics of Common Disease, Imperial College London, London, UK.
26
Department of Epidemiology and Biostatistics, Imperial College London, London, UK. m.chadeau@imperial.ac.uk.
27
MRC-PHE Centre for Environment and Health, Imperial College London, London, UK. m.chadeau@imperial.ac.uk.

Abstract

BACKGROUND:

Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.

METHODS:

DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.

RESULTS:

We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10-8 to 3.27×10-18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10-7), higher triglyceride levels (P = 5.37×10-9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10-10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10-3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10-3), independently of obesity and established risk factors.

CONCLUSION:

Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

PMID:
29713043
DOI:
10.1038/s41366-018-0064-7

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center