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

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

Wahl, Simone (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt.

Drong, Alexander (författare): Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.

Lehne, Benjamin (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.

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Loh, Marie (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Inst Hlth Sci, POB 5000, FI-90014 Oulu, Finland.;Translat Lab Genet Med TLGM, Agcy Sci, Technol & Res ASTAR, 8A Biomed Grove, Singapore 138648, Singapore.

Scott, William R. (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.

Kunze, Sonja (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.

Tsai, Pei-Chien (författare): Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.

Ried, Janina S. (författare): German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.

Zhang, Weihua (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.

Yang, Youwen (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.

Tan, Sili (författare)

Fiorito, Giovanni (författare): Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy.

Franke, Lude (författare): Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands.

Guarrera, Simonetta (författare): Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy.

Kasela, Silva (författare): Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Riia 23, EE-51010 Tartu, Estonia.

Kriebel, Jennifer (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.

Richmond, Rebecca C. (författare): Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.

Adamo, Marco (författare): Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.

Afzal, Uzma (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.

Ala-Korpela, Mika (författare): Univ Oulu & Biocenter Oulu, Computat Med, Fac Med, Oulu, Finland.;Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio, Finland.;Univ Bristol & Med Res Council Integrat Epidemiol, Univ Bristol, Sch Social & Community Med, Computat Med, Bristol, Avon, England.

Albetti, Benedetta (författare): Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.

Ammerpohl, Ole (författare): Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel Campus, Kiel, Germany.

Apperley, Jane F. (författare): Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England.

Beekman, Marian (författare): Leiden Univ Med Ctr, Mol Epidemiol, NL-2333 ZC Leiden, Netherlands.

Bertazzi, Pier Alberto (författare): Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.

Black, S. Lucas (författare): Imperial Coll London, Dept Med, Sect Infect Dis & Immun, London W12 0NN, England.

Blancher, Christine (författare)

Bonder, Marc-Jan (författare): Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands.

Brosch, Mario (författare): Univ Oxford, High Throughput Genom Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Tech Univ Dresden, Univ Hosp, Med Dept 1, Dresden, Germany.

Carstensen-Kirberg, Maren (författare): Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.

de Craen, Anton J. M. (författare): Leiden Univ Med Ctr, Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands.

de Lusignan, Simon (författare): Univ Surrey, Dept Clin & Expt Med, Guildford GU2 7PX, Surrey, England.

Dehghan, Abbas (författare): Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.

Elkalaawy, Mohamed (författare): Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt.

Fischer, Krista (författare): Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.

Franco, Oscar H. (författare): Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.

Gaunt, Tom R. (författare): Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.

Hampe, Jochen (författare): Univ Oxford, High Throughput Genom Oxford Genom Ctr, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.

Hashemi, Majid (författare): Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.

Isaacs, Aaron (författare): Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.

Jenkinson, Andrew (författare): Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.

Jha, Sujeet (författare): Dept Endocrinol, Diabet & Obes, Max Healthcare, New Delhi 110017, India.

Kato, Norihiro (författare): Res Inst, Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Tokyo 1628655, Japan.

Krogh, Vittorio (författare): Epidemiol & Prevent Unit, Fondazione IRCSS Ist Nazl Tumori, Milan, Italy.

Laffan, Michael (författare): Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England.

Meisinger, Christa (författare): Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.

Meitinger, Thomas (författare): German Res Ctr Environm Hlth, Int Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Munich, Germany.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.

Mok, Zuan Yu (författare): Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore.

Motta, Valeria (författare): Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.

Ng, Hong Kiat (författare): Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore.

Nikolakopoulou, Zacharoula (författare): Natl Heart & Lung Inst, London SW3 6LY, England.

Nteliopoulos, Georgios (författare): Imperial Coll London, Dept Med, Centre Haematol, Fac Med, Hammersmith Campus, London W12 0NN, England.

Panico, Salvatore (författare): Dipartmento Med Clin Chirurgia Federio II Univ, Naples, Italy.

Pervjakova, Natalia (författare): Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Riia 23, EE-51010 Tartu, Estonia.

Prokisch, Holger (författare): Tech Univ Munich, Inst Human Genet, Munich, Germany.

Rathmann, Wolfgang (författare): Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Biometr & Epidemiol, Dusseldorf, Germany.

Roden, Michael (författare): German Ctr Diabet Res DZD, Neuherberg, Germany.;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.;Heinrich Heine Univ Hosp Dusseldorf, Fac Med, Dept Endocrinol & Diabetol, Dusseldorf, Germany.

Rota, Federica (författare): Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.

Rozario, Michelle Ann (författare)

Sandling, Johanna K. (författare): Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab,Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.

Schafmayer, Clemens (författare): Univ Hosp Schleswig Holstein, Dept Visceral & Thorac Surg, Kiel Campus, Kiel, Germany.

Schramm, Katharina (författare): Tech Univ Munich, Inst Human Genet, Munich, Germany.

Siebert, Reiner (författare): Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel Campus, Kiel, Germany.;Univ Hosp Ulm, Inst Human Genet, Albert Einstein Allee 11, D-89081 Ulm, Germany.

Slagboom, P. Eline (författare): Leiden Univ Med Ctr, Mol Epidemiol, NL-2333 ZC Leiden, Netherlands.

Soininen, Pasi (författare): Univ Oulu & Biocenter Oulu, Computat Med, Fac Med, Oulu, Finland.;Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio, Finland.

Stolk, Lisette (författare): Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.

Strauch, Konstantin (författare): German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat, Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany.

Tai, E-Shyong (författare): Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.;Duke Natl Univ, Singapore Grad Med Sch, Singapore 169857, Singapore.

Tarantini, Letizia (författare): Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.

Thorand, Barbara (författare): Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.

Tigchelaar, Ettje F. (författare): Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands.

Tumino, Rosario (författare): Cancer Registry & Histopathol Unit, Civile MP Arezzo Hosp, ASP 7, Ragusa, Italy.

Uitterlinden, Andre G. (författare): Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands.

van Duijn, Cornelia (författare): Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.

van Meurs, Joyce B. J. (författare): Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.

Vineis, Paolo (författare): Imperial Coll London, Epidemiol & Publ Hlth, London, England.

Wickremasinghe, Ananda Rajitha (författare): Univ Kelaniya, Dept Publ Hlth, Fac Med, Box 6,Thalagolla Rd, Ragama 11010, Sri Lanka.

Wijmenga, Cisca (författare): Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands.

Yang, Tsun-Po (författare)

Yuan, Wei (författare): Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Inst Canc Res, Surrey SM2 5NG, England.

Zhernakova, Alexandra (författare): Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands.;Univ Groningen, NL-9700 AB Groningen, Netherlands.

Batterham, Rachel L. (författare): Univ Coll London Hosp, UCLH Bariatr Ctr Weight Loss, Weight Management & Metab & Endocrine Surg, Ground Floor West Wing,250 Euston Rd, London NW1 2PG, England.;UCL, Rayne Inst, Dept Med, Ctr Obes Res, London WC1E 6JJ, England.

Smith, George Davey (författare): Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.

Deloukas, Panos (författare): Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Jawhara Brahim Ctr Excellence Res Heredi, Jeddah 21589, Saudi Arabia.

Heijmans, Bastiaan T. (författare)

Herder, Christian (författare): German Ctr Diabet Res DZD, Neuherberg, Germany.;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Leibniz Ctr Diabet Res, Inst Clin Diabetol, Dusseldorf, Germany.

Hofman, Albert (författare): Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.

Lindgren, Cecilia M. (författare): Broad Inst, Massachusetts Inst Technol & Harvard Univ, Cambridge, MA 02142 USA.

Milani, Lili (författare): Univ Tartu, Estonian Genome Ctr, Riia 23b, EE-51010 Tartu, Estonia.

van der Harst, Pim (författare): Univ Med Ctr Groningen, Dept Cardiol, Univ Groningen, NL-9700 RB Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-3511 GC Utrecht, Netherlands.

Peters, Annette (författare): German Ctr Diabet Res DZD, Neuherberg, Germany.;Partner site Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany.

Illig, Thomas (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Feodor Lynen St 15, Hannover, Germany.;Hannover Med Sch, Inst Human Genet, Carl Neuberg St 1, Hannover, Germany.

Relton, Caroline L. (författare): Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.

Waldenberger, Melanie (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.

Jaervelin, Marjo-Riitta (författare): Imperial Coll London, Sch Publ Hlth, MRC Hlth Protect Agcy HPE Ctr Environm & Hlth, Dept Epidemiol & Biostatist, London, England.;Univ Oulu, Bioctr Oulu, POB 5000, Oulu, Finland.;Univ Oulu, Ctr Life Course Epidemiol, Fac Med, POB 5000, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Care, Kajaanintie 50,Box 20, Oulu, Finland.

Bollati, Valentina (författare): Univ Studi Milano & Fondazione IRCCS CaGranda Osp, Dept Clin Sci & Community Hlth, EPIGET Lab, Milan, Italy.

Soong, Richie (författare): Natl Univ Singapore, Cancer Sci Inst Singapore, Singapore, Singapore.;Natl Univ Singapore Hosp, Dept Pathol, Singapore, Singapore.

Spector, Tim D. (författare): Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.

Scott, James (författare): Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.

McCarthy, Mark I. (författare): Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford NIHR Biomed Res Ctr, Churchill Hosp, Oxford OX3 7LJ, England.

Elliott, Paul (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.

Bell, Jordana T. (författare): Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.

Matullo, Giuseppe (författare): Human Genet Fdn Torino, Turin, Italy.;Univ Torino, Dept Med Sci, Turin, Italy.

Gieger, Christian (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.

Kooner, Jaspal S. (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.;Imperial Coll Healthcare NHS Trust, London W12 0HS, England.

Grallert, Harald (författare): Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.

Chambers, John C. (författare): Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostatist, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.;Imperial Coll London, Natl Heart & Lung Inst, London W12 0NN, England.;Ealing Hosp NHS Trust, Middlesex UB1 3HW, England.;Imperial Coll Healthcare NHS Trust, London W12 0HS, England.;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.

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Res Unit Mol Epidemiol, German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Neuherberg, Germany;Inst Epidemiol II, German Res Ctr Environm Hlth, Helmholtz Zentrum M nchen, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Alexandria, Med Res Inst, Clin & Expt Surg Dept, Hadara, Alexandria 21561, Egypt. Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. (creator_code:org_t)

NATURE PUBLISHING GROUP, 2017
2017
Engelska.
Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7635, s. 81-

Relaterad länk:: https://doi.org/10.1...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

Stäng

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.