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Wahl, S. ; Drong, A.* ; Lehne, B.* ; Loh, M.* ; Scott, W.R.* ; Kunze, S. ; Tsai, P.C.* ; Ried, J.S. ; Zhang, W.* ; Yang, Y.* ; Tan, S.* ; Fiorito, G.* ; Franke, L.* ; Guarrera, S.* ; Kasela, S.* ; Kriebel, J. ; Richmond, R.C.* ; Adamo, M.* ; Afzal, U.* ; Ala-Korpela, M.* ; Albetti, B.* ; Ammerpohl, O.* ; Apperley, J.* ; Beekman, M.* ; Bertazzi, P.A.* ; Black, S.L.* ; Blancher, C.* ; Bonder, M.J.* ; Brosch, M.* ; Carstensen-Kirberg, M.* ; de Craen, A.J.M.* ; de Lusignan, S.* ; Dehghan, A.* ; Elkalaawy, M.* ; Fischer, K.* ; Franco, O.H.* ; Gaunt, T.R.* ; Hampe, J.* ; Hashemi, M* ; Isaacs, A.* ; Jenkinson, A.* ; Jha, S.* ; Kato, N.* ; Krogh, V.* ; Laffan, M.* ; Meisinger, C. ; Meitinger, T. ; Mok, Z.Y.* ; Motta, V.* ; Ng, H.K.* ; Nikolakopoulou, Z.* ; Nteliopoulos, G.* ; Panico, S.* ; Pervjakova, N.* ; Prokisch, H. ; Rathmann, W.* ; Roden, M.* ; Rota, F.* ; Rozario, M.A.* ; Sandling, J.K.* ; Schafmayer, C.* ; Schramm, K. ; Siebert, R.* ; Slagboom, P.E.* ; Soininen, P.* ; Stolk, L.* ; Strauch, K. ; Tai, E.S.* ; Tarantini, L.* ; Thorand, B. ; Tigchelaar, E.F.* ; Tumino, R.* ; Uitterlinden, A.G.* ; van Duijn, C.M.* ; van Meurs, J.B.J.* ; Vineis, P.* ; Wichremasinghe, A.R.* ; Wijmenga, C* ; Yang, T.P.* ; Yuan, W.* ; Zhernakova, A.* ; Batterham, R.* ; Smith, G.D.* ; Deloukas, P.* ; Heijman, B.T.* ; Herder, C.* ; Hofman, A.* ; Lindgren, C.M.* ; Milani, L.* ; van der Harst, P.* ; Peters, A. ; Illig, T. ; Relton, C.L.* ; Waldenberger, M. ; Järvelin, M.-R.* ; Bollati, V.* ; Soong, R.* ; Spector, T.D.* ; Scott, J.* ; McCarthy, M.I.* ; Elliott, P.* ; Bell, J.T.* ; Matullo, G.* ; Gieger, C. ; Kooner, J.S.* ; Grallert, H. ; Chambers, J.C.*

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

Nature 541, 81-86 (2017)
Postprint Research data DOI PMC
Open Access Green
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, 4, 5, 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dna Methylation; Mendelian Randomization; Bariatric Surgery; Disease; Obesity; Glucose; Humans; Health; Trends; Tissue
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 541, Issue: 7635, Pages: 81-86 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)