Altmetric

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

File Description SizeFormat 
Nature 2015-03-03573E - Supplementary tables.xlsxSupporting information14.34 MBUnknownView/Open
Nature 2015-03-03573E - Main.pdfAccepted version529.22 kBAdobe PDFView/Open
Nature 2015-03-03573E - supplementary info.pdfSupporting information3.31 MBAdobe PDFView/Open
Title: Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
Authors: Wahl, S
Drong, A
Lehne, B
Loh, M
Scott, WR
Kunze, S
Tsai, P-C
Ried, JS
Zhang, W
Yang, Y
Tan, S
Fiorito, G
Franke, L
Guarrera, S
Kasela, S
Kriebel, J
Richmond, RC
Adamo, M
Afzal, U
Ala-Korpela, M
Albetti, B
Ammerpohl, O
Apperley, JF
Beekman, M
Bertazzi, PA
Black, SL
Blancher, C
Bonder, M-J
Brosch, M
Carstensen-Kirberg, M
De Craen, AJM
De Lusignan, S
Dehghan, A
Elkalaawy, M
Fischer, K
Franco, OH
Gaunt, TR
Hampe, J
Hashemi, M
Isaacs, A
Jenkinson, A
Jha, S
Kato, N
Krogh, V
Laffan, M
Meisinger, C
Meitinger, T
Mok, ZY
Motta, V
Ng, HK
Nikolakopoulou, Z
Nteliopoulos, G
Panico, S
Pervjakova, N
Prokisch, H
Rathmann, W
Roden, M
Rota, F
Rozario, MA
Sandling, JK
Schafmayer, C
Schramm, K
Siebert, R
Slagboom, PE
Soininen, P
Stolk, L
Strauch, K
Tai, E-S
Tarantini, L
Thorand, B
Tigchelaar, EF
Tumino, R
Uitterlinden, AG
Van Duijn, C
Van Meurs, JBJ
Vineis, P
Wickremasinghe, AR
Wijmenga, C
Yang, T-P
Yuan, W
Zhernakova, A
Batterham, RL
Smith, GD
Deloukas, P
Heijmans, BT
Herder, C
Hofman, A
Lindgren, CM
Milani, L
Van der Harst, P
Peters, A
Illig, T
Relton, CL
Waldenberger, M
Jaervelin, M-R
Bollati, V
Soong, R
Spector, TD
Scott, J
McCarthy, MI
Elliott, P
Bell, JT
Matullo, G
Gieger, C
Kooner, JS
Grallert, H
Chambers, JC
Item Type: Journal Article
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 disturbances1,2 . Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation3–6, a key regulator of gene expression and molecular phenotype7 . 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
Issue Date: 21-Dec-2016
Date of Acceptance: 10-Nov-2016
URI: http://hdl.handle.net/10044/1/49547
DOI: https://dx.doi.org/10.1038/nature20784
ISSN: 0028-0836
Publisher: Nature Publishing Group
Start Page: 81
End Page: +
Journal / Book Title: Nature
Volume: 541
Issue: 7635
Copyright Statement: © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Sponsor/Funder: British Heart Foundation
Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
National Institute for Health Research
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Action on Hearing Loss
British Society For Haematology
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: SP/04/02
G0700931
084723/Z/08/Z
G0601966
NF-SI-0611-10136
MC_G0802523
RDC01 79560
G51_Chambers
N/A
MR/K002414/1
RDB05 79560
NF-SI-0611-10275
RDB05 79560
MR/L01341X/1
RTJ6219303-1
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
DNA METHYLATION
MENDELIAN RANDOMIZATION
BARIATRIC SURGERY
DISEASE
OBESITY
GLUCOSE
HUMANS
HEALTH
TRENDS
TISSUE
Adipose Tissue
Adiposity
Asian Continental Ancestry Group
Blood
Body Mass Index
Cohort Studies
DNA Methylation
Diabetes Mellitus, Type 2
Epigenesis, Genetic
Epigenomics
Europe
European Continental Ancestry Group
Female
Genetic Markers
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
India
Male
Obesity
Overweight
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Epidemiology, Public Health and Primary Care



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons