Show simple item record

dc.date.accessioned2018-07-05T11:24:59Z
dc.date.issued2017
dc.identifierhttp://publications.icr.ac.uk/15755/
dc.identifier.citationNATURE, 2017, 541 (7635), pp. 81 - 86
dc.identifier.issn0028-0836
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1998
dc.description.abstractApproximately 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(1,2). Although the mechanisms linking adiposity to associated clinical conditions 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 with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 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 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 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 x 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.
dc.format.extent81 - 86
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectDNA METHYLATION MENDELIAN RANDOMIZATION BARIATRIC SURGERY DISEASE OBESITY GLUCOSE HUMANS HEALTH TRENDS TISSUE
dc.titleEpigenome-wide association study of body mass index, and the adverse outcomes of adiposity
dc.typeJournal Article
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNATURE
pubs.issue7635
pubs.notesISI Document Delivery No.: EN6NA Times Cited: 2 Cited Reference Count: 30 Wahl, Simone Drong, Alexander Lehne, Benjamin Loh, Marie Scott, William R. Kunze, Sonja Tsai, Pei-Chien Ried, Janina S. Zhang, Weihua Yang, Youwen Tan, Sili Fiorito, Giovanni Franke, Lude Guarrera, Simonetta Kasela, Silva Kriebel, Jennifer Richmond, Rebecca C. Adamo, Marco Afzal, Uzma Ala-Korpela, Mika Albetti, Benedetta Ammerpohl, Ole Apperley, Jane F. Beekman, Marian Bertazzi, Pier Alberto Black, S. Lucas Blancher, Christine Bonder, Marc-Jan Brosch, Mario Carstensen-Kirberg, Maren de Craen, Anton J. M. de Lusignan, Simon Dehghan, Abbas Elkalaawy, Mohamed Fischer, Krista Franco, Oscar H. Gaunt, Tom R. Hampe, Jochen Hashemi, Majid Isaacs, Aaron Jenkinson, Andrew Jha, Sujeet Kato, Norihiro Krogh, Vittorio Laffan, Michael Meisinger, Christa Meitinger, Thomas Mok, Zuan Yu Motta, Valeria Ng, Hong Kiat Nikolakopoulou, Zacharoula Nteliopoulos, Georgios Panico, Salvatore Pervjakova, Natalia Prokisch, Holger Rathmann, Wolfgang Roden, Michael Rota, Federica Rozario, Michelle Ann Sandling, Johanna K. Schafmayer, Clemens Schramm, Katharina Siebert, Reiner Slagboom, P. Eline Soininen, Pasi Stolk, Lisette Strauch, Konstantin Tai, E-Shyong Tarantini, Letizia Thorand, Barbara Tigchelaar, Ettje F. Tumino, Rosario Uitterlinden, Andre G. van Duijn, Cornelia van Meurs, Joyce B. J. Vineis, Paolo Wickremasinghe, Ananda Rajitha Wijmenga, Cisca Yang, Tsun-Po Yuan, Wei Zhernakova, Alexandra Batterham, Rachel L. Smith, George Davey Deloukas, Panos Heijmans, Bastiaan T. Herder, Christian Hofman, Albert Lindgren, Cecilia M. Milani, Lili van der Harst, Pim Peters, Annette Illig, Thomas Relton, Caroline L. Waldenberger, Melanie Jaervelin, Marjo-Riitta Bollati, Valentina Soong, Richie Spector, Tim D. Scott, James McCarthy, Mark I. Elliott, Paul Bell, Jordana T. Matullo, Giuseppe Gieger, Christian Kooner, Jaspal S. Grallert, Harald Chambers, John C. 2 NATURE PUBLISHING GROUP LONDON NATURE none 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(1,2). Although the mechanisms linking adiposity to associated clinical conditions 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 with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 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 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 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 x 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.
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.volume541
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
dc.contributor.icrauthorYuan, Weien


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record