Six new loci associated with body mass index highlight a neuronal influence on body weight regulation (original) (raw)

References

  1. Flegal, K.M., Graubard, B.I., Williamson, D.F. & Gail, M.H. Cause-specific excess deaths associated with underweight, overweight, and obesity. J. Am. Med. Assoc. 298, 2028–2037 (2007).
    Article CAS Google Scholar
  2. Finkelstein, E.A. et al. The lifetime medical cost burden of overweight and obesity: implications for obesity prevention. Obesity (Silver Spring) 16, 1843–1848 (2008).
    Article Google Scholar
  3. Maes, H.H., Neale, M.C. & Eaves, L.J. Genetic and environmental factors in relative body weight and human adiposity. Behav. Genet. 27, 325–351 (1997).
    Article CAS Google Scholar
  4. Atwood, L.D. et al. Genomewide linkage analysis of body mass index across 28 years of the Framingham Heart Study. Am. J. Hum. Genet. 71, 1044–1050 (2002).
    Article CAS Google Scholar
  5. Farooqi, I.S. Genetic aspects of severe childhood obesity. Pediatr. Endocrinol. Rev. 3 (Suppl. 4), 528–536 (2006).
    PubMed Google Scholar
  6. Scuteri, A. et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 3, e115 (2007).
    Article Google Scholar
  7. Frayling, T.M. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894 (2007).
    Article CAS Google Scholar
  8. Dina, C. et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat. Genet. 39, 724–726 (2007).
    Article CAS Google Scholar
  9. Loos, R.J. et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 40, 768–775 (2008).
    Article CAS Google Scholar
  10. Chambers, J.C. et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat. Genet. 40, 716–718 (2008).
    Article CAS Google Scholar
  11. Benzinou, M. et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat. Genet. 40, 943–945 (2008).
    Article CAS Google Scholar
  12. Thorleifsson, G. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. advance online publication, doi:10.1038/ng.274 (14 December 2008).
  13. Herbert, A. et al. A common genetic variant is associated with adult and childhood obesity. Science 312, 279–283 (2006).
    Article CAS Google Scholar
  14. Liu, Y.J. et al. Genome-wide association scans identified CTNNBL1 as a novel gene for obesity. Hum. Mol. Genet. 17, 1803–1813 (2008).
    Article CAS Google Scholar
  15. Zeggini, E. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638–645 (2008).
    Article CAS Google Scholar
  16. Willer, C.J. et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet. 40, 161–169 (2008).
    Article CAS Google Scholar
  17. Samani, N.J. et al. Genomewide association analysis of coronary artery disease. N. Engl. J. Med. 357, 443–453 (2007).
    Article CAS Google Scholar
  18. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).
  19. Freathy, R.M. et al. Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes 57, 1419–1426 (2008).
    Article CAS Google Scholar
  20. McCarroll, S.A. et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet. 40, 1166–1174 (2008).
    Article CAS Google Scholar
  21. Ren, D. et al. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. J. Clin. Invest. 117, 397–406 (2007).
    Article CAS Google Scholar
  22. Pagliarini, D.J. et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell 134, 112–123 (2008).
    Article CAS Google Scholar
  23. Grinberg, M. et al. Mitochondrial carrier homolog 2 is a target of tBID in cells signaled to die by tumor necrosis factor alpha. Mol. Cell. Biol. 25, 4579–4590 (2005).
    Article CAS Google Scholar
  24. Marg, A. et al. Neurotractin, a novel neurite outgrowth-promoting Ig-like protein that interacts with CEPU-1 and LAMP. J. Cell Biol. 145, 865–876 (1999).
    Article CAS Google Scholar
  25. Schafer, M., Brauer, A.U., Savaskan, N.E., Rathjen, F.G. & Brummendorf, T. Neurotractin/kilon promotes neurite outgrowth and is expressed on reactive astrocytes after entorhinal cortex lesion. Mol. Cell. Neurosci. 29, 580–590 (2005).
    Article Google Scholar
  26. Rankinen, T. et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 14, 529–644 (2006).
    Article Google Scholar
  27. Myers, A.J. et al. A survey of genetic human cortical gene expression. Nat. Genet. 39, 1494–1499 (2007).
    Article CAS Google Scholar
  28. Bramham, C.R. & Messaoudi, E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Prog. Neurobiol. 76, 99–125 (2005).
    Article CAS Google Scholar
  29. Unger, T.J., Calderon, G.A., Bradley, L.C., Sena-Esteves, M. & Rios, M. Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J. Neurosci. 27, 14265–14274 (2007).
    Article CAS Google Scholar
  30. Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141 (1997).
    Article CAS Google Scholar
  31. Marsh, D.J. et al. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21, 119–122 (1999).
    Article CAS Google Scholar
  32. Stratigopoulos, G. et al. Regulation of Fto/Ftm gene expression in mice and humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R1185–R1196 (2008).
    Article CAS Google Scholar
  33. Gerken, T. et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318, 1469–1472 (2007).
    Article CAS Google Scholar
  34. Li, Z., Zhou, Y., Carter-Su, C., Myers, M.G. Jr & Rui, L. SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms. Mol. Endocrinol. 21, 2270–2281 (2007).
    Article CAS Google Scholar
  35. Fritschy, J.M. & Mohler, H. GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits. J. Comp. Neurol. 359, 154–194 (1995).
    Article CAS Google Scholar
  36. Fehr, C. et al. Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Psychiatr. Genet. 16, 9–17 (2006).
    Article Google Scholar
  37. Covault, J., Gelernter, J., Hesselbrock, V., Nellissery, M. & Kranzler, H.R. Allelic and haplotypic association of GABRA2 with alcohol dependence. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 129B, 104–109 (2004).
    Article Google Scholar
  38. Edenberg, H.J. et al. Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am. J. Hum. Genet. 74, 705–714 (2004).
    Article CAS Google Scholar
  39. Berthoud, H.R. & Morrison, C. The brain, appetite, and obesity. Annu. Rev. Psychol. 59, 55–92 (2008).
    Article Google Scholar
  40. Cartegni, L., Wang, J., Zhu, Z., Zhang, M.Q. & Krainer, A.R. ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res. 31, 3568–3571 (2003).
    Article CAS Google Scholar
  41. Sureau, A., Gattoni, R., Dooghe, Y., Stevenin, J. & Soret, J. SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs. EMBO J. 20, 1785–1796 (2001).
    Article CAS Google Scholar
  42. Dixon, A.L. et al. A genome-wide association study of global gene expression. Nat. Genet. 39, 1202–1207 (2007).
    Article CAS Google Scholar
  43. Weedon, M.N. et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nat. Genet. 40, 575–583 (2008).
    Article CAS Google Scholar
  44. Lettre, G. et al. Identification of ten loci associated with height highlights new biological pathways in human growth. Nat. Genet. 40, 584–591 (2008).
    Article CAS Google Scholar
  45. Winckler, W. et al. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes 56, 685–693 (2007).
    Article CAS Google Scholar
  46. Bonnycastle, L.L. et al. Common variants in maturity-onset diabetes of the young genes contribute to risk of type 2 diabetes in Finns. Diabetes 55, 2534–2540 (2006).
    Article CAS Google Scholar
  47. Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).
    Article CAS Google Scholar
  48. Abecasis, G.R., Cherny, S.S., Cookson, W.O. & Cardon, L.R. Merlin–rapid analysis of dense genetic maps using sparse gene flow trees. Nat. Genet. 30, 97–101 (2002).
    Article CAS Google Scholar
  49. Chen, W.M. & Abecasis, G.R. Family-based association tests for genomewide association scans. Am. J. Hum. Genet. 81, 913–926 (2007).
    Article CAS Google Scholar

Download references

Acknowledgements

We are extremely grateful to all of the participants in each of the studies contributing to this effort. Full acknowledgments can be found in the Supplementary Note.

Support for this research was provided by: US National Institutes of Health grants CA65725, CA87969, CA49449, CA67262, CA50385, DK062370, DK072193, DK075787, HG02651, HL084729, HL087679 (through STAMPEED, 1RL1MH083268), 5UO1CA098233, 1Z01 HG000024, 1RL1MH083268, T32 DK07191, F32 DK079466, K23 DK080145, K23 DK067288, CIDR NIH Contract Number N01-HG-65403, NIA contract NO1-AG-1-2109; the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; contracts from the Division of Cancer Prevention, National Cancer Institute and EU FP6 funding (contract no LSHM-CT-2003-503041); GlaxoSmithKline; the Faculty of Biology and Medicine of Lausanne, Switzerland; the Intramural Research Program of the National Institute on Aging (NIA); Cancer Research United Kingdom; the UK Medical Research Council (including grants G0000649, G0000934 and G0601261); the Wellcome Trust (including Strategic Award 076113, grants 068545/Z/02 and 076467/Z/05/Z); the NIHR through the Biomedical Research Centres at Oxford, King's College London; Guys and St. Thomas' Foundation Hospitals' Trust; the British Heart Foundation (including grant FS/05/061/19501), European Community's Seventh Framework Programme (ENGAGE:HEALTH-F4-2007-201413); Diabetes UK; Unilever Corporate Research; American Diabetes Association including a Smith Family Foundation Pinnacle Program Project Award #7-03-PPG-04R; the Academy of Finland (grants 118065 and 124243); National Genome Research Net Germany; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; the Helmholtz Center Munich; the Sigrid Juselius Foundation; University of Bristol; Linné grant from Swedish Research Council; Wallenberg Foundation; Folkhälsan Research Foundation; University of Southampton; Netherlands Organisation of Scientific Research NWO (nr. 175.010.2005.011); Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Ministry of Education, Culture and Science; the Netherlands Ministry for Health, Welfare and Sports; the European Commision (DG XII) and the Municipality of Rotterdam. G.R.A. and K.L.M. are Pew Scholars for the Biomedical Sciences; A.L.E. is supported by a Sarnoff Cardiovascular Research Foundation Fellowship; C.M.L. is a Nuffield Department of Medicine Scientific Leadership Fellow; S.A.M. is supported by a Life Sciences Research Fellowship; M.K. is supported by the Finnish Cultural Foundation; N.J.S. holds a BHF Chair; M.N.W. is a Vandervell Foundation Research Fellow; C.J.W. is supported by an American Diabetes Association postdoctoral fellowship; and E.Z. is a Wellcome Trust-RD Fellow (grant number 079557).

Author information

Author notes

  1. A full list of members is provided in the Supplementary Note online.
  2. Cristen J Willer, Elizabeth K Speliotes, Ruth J F Loos and Shengxu Li: These authors contributed equally to this work.
  3. Cristen J Willer, Elizabeth K Speliotes, Ruth J F Loos, Shengxu Li, Cecilia M Lindgren, Iris M Heid, Mark I McCarthy, Michael Boehnke, Inês Barroso, Gonçalo R Abecasis and Joel N Hirschhorn: Members of the writing team.
  4. Mark I McCarthy, Michael Boehnke, Inês Barroso, Gonçalo R Abecasis and Joel N Hirschhorn: These authors jointly directed the project.

Authors and Affiliations

  1. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Cristen J Willer, Anne U Jackson, Laura J Scott, Heather M Stringham & Michael Boehnke
  2. Division of Gastroenterology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
    Elizabeth K Speliotes
  3. Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, 02142, Massachusetts, USA
    Elizabeth K Speliotes, Helen N Lyon & Joel N Hirschhorn
  4. Medical Research Council Epidemiology Unit, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
    Ruth J F Loos, Shengxu Li, Jing Hua Zhao, Christopher J Gillson, Jian'an Luan, Manjinder S Sandhu, Matthew A Sims, Karani S Vimaleswaran, Ken K Ong & Nicholas J Wareham
  5. Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
    Ruth J F Loos, Shengxu Li, Jing Hua Zhao, Christopher J Gillson, Zorica Jovanovic, Jian'an Luan, Stephen O'Rahilly, Carolin Purmann, Matthew A Sims, Y C Loraine Tung, Karani S Vimaleswaran, I Sadaf Farooqi, Ken K Ong & Nicholas J Wareham
  6. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
    Cecilia M Lindgren, Joshua C Randall, Inga Prokopenko, Eleftheria Zeggini & Mark I McCarthy
  7. Institute of Epidemiology, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, Neuherberg, 85764, Germany
    Iris M Heid, Claudia Lamina, Christian Gieger & H-Erich Wichmann
  8. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA
    Sonja I Berndt, Stephen J Chanock & Richard B Hayes
  9. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, 02142, Massachusetts, USA
    Amanda L Elliott, Guillaume Lettre, Steven A McCarroll, Noël P Burtt, Lauren Gianniny, Candace Guiducci, Rachel Hackett, Mikko Kuokkanen, David Altshuler, David J Hunter & Leena Peltonen
  10. Department of Molecular Biology, Massachusetts General Hospital, Cambridge, 02144, Massachusetts, USA
    Amanda L Elliott, Steven A McCarroll & David Altshuler
  11. Program in Genomics and Divisions of Endocrinology and Genetics, Children's Hospital, Boston, 02115, Massachusetts, USA
    Guillaume Lettre, Helen N Lyon & Joel N Hirschhorn
  12. Medical Genetics/Clinical Pharmacology and Discovery Medicine, King of Prussia, 19406, Pennsylvania, USA
    Noha Lim, Kijoung Song, Dawn M Waterworth & Vincent Mooser
  13. Division of Community Health Sciences, St. George's, University of London, London, SW17 0RE, UK
    Konstantinos Papadakis, David Hadley & David P Strachan
  14. Department of Nutrition, Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Lu Qi, Frank B Hu & David J Hunter
  15. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Boston, 02115, Massachusetts, USA
    Lu Qi, Frank B Hu & David J Hunter
  16. Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK
    Rosa Maria Roccasecca, Eleanor Wheeler, Nicole Soranzo, Willem H Ouwehand, Panagiotis Deloukas, Leena Peltonen & Inês Barroso
  17. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, 09042, Italy
    Serena Sanna, Antonella Mulas & Manuela Uda
  18. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Paul Scheet & Gonçalo R Abecasis
  19. Genetics of Complex Traits, Peninsula Medical School, Exeter, EX1 2LU, UK
    Michael N Weedon & Timothy M Frayling
  20. Department of Internal Medicine, Erasmus MC, PO Box 2400, Rotterdam, NL-3000-CA, The Netherlands
    Leonie C Jacobs, Karol Estrada, Fernando Rivadeneira, M Carola Zillikens & André G Uitterlinden
  21. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.,
    Inga Prokopenko & Mark I McCarthy
  22. Department of Twin Research and Genetic Epidemiology, King's College London, London, SE1 7EH, UK
    Nicole Soranzo, Guangju Zhai & Timothy D Spector
  23. National Institute of Aging, Clinical Research Branch - Longitudinal Studies Section, Baltimore, 21225, Maryland, USA
    Toshiko Tanaka & Luigi Ferrucci
  24. Department of Social Medicine, MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, BS8 2PR, UK
    Nicholas J Timpson, George Davey Smith & David M Evans
  25. Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, 20502, Sweden
    Peter Almgren & Leif C Groop
  26. DRL, OCDEM, Churchill Hospital, Headington, OX3 7LJ, Oxford, UK
    Amanda Bennett
  27. Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles, 90033, California, USA
    Richard N Bergman
  28. MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Cambridge, CB2 0XY, UK
    Sheila A Bingham
  29. MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Cambridge, CB1 8RN, UK
    Sheila A Bingham
  30. National Human Genome Research Institute, Bethesda, 20892, Maryland, USA
    Lori L Bonnycastle, Peter Chines, Francis S Collins, Parimal Deodhar, Michael R Erdos, Narisu Narisu & Matthew G Rees
  31. Cambridge, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, CB2 0QQ, UK
    Morris Brown
  32. Department of Epidemiology and Public Health, Imperial College London, St. Mary's Campus, Norfolk Place, London, W2 1PG, UK
    Lachlan Coin, Paul Elliott & Marjo-Riitta Jarvelin
  33. British Heart Foundation Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow, G12 8TA, UK
    John M Connell
  34. MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK
    Cyrus Cooper & Elaine M Dennison
  35. Yorkshire Heart Centre, Leeds General Infirmary, Leeds, LS1 3EX, UK
    Alistair S Hall
  36. KTL-National Public Health Institute, Helsinki, FI-00300, Finland
    Aki S Havulinna, Pekka Jousilahti & Veikko Salomaa
  37. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Virchowstr. 174, Essen, 45147, Germany
    Johannes Hebebrand
  38. Department of Epidemiology, Erasmus MC, PO Box 2400, Rotterdam, NL-3000-CA, The Netherlands
    Albert Hofman, Fernando Rivadeneira, Cornelia M Van Duijn, Jacqueline C M Witteman & André G Uitterlinden
  39. Folkhalsan Research Center, Malmska Municipal Health Center and Hospital, Jakobstad, FIN-00014, Finland
    Bo Isomaa
  40. Bioinformed Consulting Services, Gaithersburg, 20877, Maryland, USA
    Kevin B Jacobs
  41. Department of Medical Genetics, University of Lausanne, Lausanne, CH-1005, Switzerland
    Toby Johnson
  42. University Institute for Social and Preventative Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, CH-1005, Switzerland
    Toby Johnson
  43. Swiss Institute of Bioinformatics, Lausanne, CH-1005, Switzerland
    Toby Johnson
  44. University of Cambridge Metabolic Research Laboratories, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
    Zorica Jovanovic, Stephen O'Rahilly, Carolin Purmann, Y C Loraine Tung & I Sadaf Farooqi
  45. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, CB2 0SR, UK
    Kay-Tee Khaw, Robert N Luben & Manjinder S Sandhu
  46. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Peter Kraft & David J Hunter
  47. Department of Molecular Medicine, National Public Health Institute, Helsinki, FIN-00300, Finland
    Mikko Kuokkanen & Kaisa Silander
  48. Department of Medicine, University of Kuopio, Kuopio, 70210, Finland
    Johanna Kuusisto & Markku Laakso
  49. Finnish Institute of Occupational Health, Aapistie 1, Oulu, Fin-90220, Finland
    Jaana Laitinen
  50. Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, 21224, Maryland, USA
    Edward G Lakatta
  51. Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences, Glenfield General Hospital, Leicester, LE3 9QP, UK
    Massimo Mangino, Suzanne Stevens & Nilesh J Samani
  52. Department of Social Medicine, Avon Longitudinal Study of Parents and Children (ALSPAC), University of Bristol, Bristol, BS8 1TQ, UK
    Wendy L McArdle, Kate Northstone & Susan M Ring
  53. Institute of Human Genetics, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, Neuherberg, 85764, Germany
    Thomas Meitinger
  54. Institute of Human Genetics, Technical University Munich, Munich, D-81765, Germany
    Thomas Meitinger
  55. Clinical Pharmacology, The William Harvey Research Institute, Bart's and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK
    Patricia B Munroe, Chris Wallace & Mark J Caulfield
  56. Department of Oral & Dental Science, University of Bristol, Bristol, BS1 2LY, UK
    Andrew R Ness
  57. Department of Clinical Sciences, Lund University, Malmö, 20502, Sweden
    Martin Ridderstråle
  58. Department of Clinical Chemistry, University of Oulu, Oulu, Fin-90220, Finland
    Aimo Ruokonen
  59. Savitaipale Health Center, Savitaipale, FIN-54800, Finland
    Jouko Saramies
  60. Unitá Operativa Geriatria, Istituto Nazionale Ricovero e Cura Anziani, Rome, 00189, Italy
    Angelo Scuteri
  61. Department of Haematology, University of Cambridge/NHS Blood & Transplant, Cambridge, CB2 2PR, UK
    Jonathan Stephens, Nicholas Watkins & Willem H Ouwehand
  62. Department of Epidemiology and Health Promotion, National Public Health Institute, Mannerheimintie 166, Helsinki, FIN-00300, Finland
    Timo T Valle & Jaakko Tuomilehto
  63. Department of Internal Medicine, BH-10 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, 1011, Switzerland
    Peter Vollenweider & Gerard Waeber
  64. Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine, University of Southern California, Los Angeles, CHP-220, 90089, California, USA
    Richard M Watanabe
  65. Laboratory of Epidemiology, Demography, and Biometry; Gerontology Research Center, National Institute on Aging, Bethesda, 20892, Maryland, USA
    Jack M Guralnik
  66. Peninsula Medical School, Exeter, EX5 2DW, UK
    Andrew T Hattersley
  67. Department of Medicine, Helsinki University Central Hospital, Helsinki, FIN-00290, Finland
    Tiinamaija Tuomi
  68. Research Program of Molecular Medicine, University of Helsinki, Helsinki, FIN-00014, Finland
    Tiinamaija Tuomi
  69. Department of Medicine, Helsinki University, Helsinki, FIN-00029, Finland
    Leif C Groop
  70. Department of Genetics, University of North Carolina, CB #7264, Chapel Hill, 27599, North Carolina, USA
    Karen L Mohlke
  71. Institute of Molecular Medicine, University of Helsinki, Helsinki, FIN-00014, Finland
    Leena Peltonen
  72. Laboratory of Genetics, US National Institutes of Health Biomedical Research Center, National Institute on Aging, Baltimore, 21224, Maryland, USA
    David Schlessinger
  73. Institute of Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-University München, Marchioninistr. 15, München, 81377, Germany
    H-Erich Wichmann
  74. National Institute for Health Research, Oxford Biomedical Research Centre, University of Oxford, Old Road, Headington, OX3 7LJ, Oxford, UK
    Mark I McCarthy
  75. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Joel N Hirschhorn

Consortia

the GIANT Consortium

Contributions

The writing team consisted of G.R.A., I.B., M.B., I.M.H., J.N.H., S.L., C.M.L., R.J.F.L., M.I.McC., E.K.S. and C.J.W. Full author contributions and roles are listed in the Supplementary Note.

Corresponding authors

Correspondence toMark I McCarthy, Michael Boehnke, Inês Barroso, Gonçalo R Abecasis or Joel N Hirschhorn.

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Competing interests

Peter Vollenweider and Gérard Waeber received financial support from GlaxoSmithKline to build the CoLaus study; Dawn Waterworth, Kijoung Song, Noha Lim and Vincent Mooser are full-time employees of GlaxoSmithKline (GSK); Inês Barroso owns stock in the companies GlaxoSmithKline (CSK) and Incyte (INCY).

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the GIANT Consortium. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.Nat Genet 41, 25–34 (2009). https://doi.org/10.1038/ng.287

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