A new highly penetrant form of obesity due to deletions on chromosome 16p11.2 (original) (raw)

Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

The expression microarray data for carriers of 16p11.2 deletions is deposited in Gene Expression Omnibus under accession number GSE19238.

References

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Acknowledgements

A.J.W., A.I.F.B. and P.F. are supported by grants from the Wellcome Trust and the Medical Research Council (MRC). J.S.B. is supported by a grant from the Swiss National Foundation (310000-112552). L.J.M.C. is supported by an RCUK Fellowship. S.J. is funded by Swiss National Fund 320030_122674 and the Synapsis Foundation, University of Lausanne. A.V. is funded by the Ludwig Institute for Cancer Research. S.B. is supported by the Swiss Institute of Bioinformatics. I.S.F. and M.E.H. are funded by the Wellcome Trust and the MRC. We thank the DHOS (Direction de l’Hospitalisation et de l’Organisation des Soins) from the French Ministry of Health for their support in the development of several array CGH platforms in France. We thank ‘le Conseil Regional Nord Pas de Calais/FEDER’ for their financial support. Part of the CoLaus computation was performed at the Vital-IT center for high-performance computing of the Swiss Institute of Bioinformatics. The CoLaus authors thank Y. Barreau, M. Firmann, V. Mayor, A.-L. Bastian, B. Ramic, M. Moranville, M. Baumer, M. Sagette, J. Ecoffey and S. Mermoud for data collection. The CoLaus study was supported by grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne and by the Swiss National Foundation (33CSCO-122661). K.M., A.K., T.E., M.N. and A.M. received support from targeted financing from Estonian Government SF0180142s08, and P.P. from SF0180026s09; and from the EU through the European Regional Development Fund. T.E., M.N. and A.M. received support from FP7 grants (201413 ENGAGE, 212111 BBMRI, ECOGENE (no. 205419, EBC)). The genotyping of the Estonian Genome Project samples were performed in the Estonian Biocentre Genotyping Core Facility. The EGPUT authors thank V. Soo for technical help in genotyping. The Northwick Park authors acknowledge support from the NIHR Biomedical Research Centre Scheme and the Hammersmith Hospital Charity Trustees. Genome Canada and Genome Quebec funded the genotyping of DESIR subjects. Work on the SOS sib pair cohort was supported by grants from the Swedish Research Council (K2008-65X-20753-01-4, K2007-55X-11285-13, 529-2002-6671), the Swedish Foundation for Strategic Research to Sahlgrenska Center for Cardiovascular and Metabolic Research, the Swedish Diabetes Foundation, the Åke Wiberg Foundation, Foundations of the National Board of Health and Welfare, the Jeansson Foundations, the Magn Bergvall Foundation, the Tore Nilson Foundation, the Royal Physiographic Society (Nilsson-Ehle Foundation), VINNOVA-VINNMER, and the Swedish federal government under the LUA/ALF agreement. The DESIR study has been supported by INSERM, CNAMTS, Lilly, Novartis Pharma and Sanofi-Aventis, by INSERM (Réseaux en Santé Publique, Interactions entre les determinants de la santé), by the Association Diabète Risque Vasculaire, the Fédération Française de Cardiologie, La Fondation de France, ALFEDIAM, ONIVINS, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche and Topcon. Northern Finland Birth Cohort 1966 (NFBC1966) was supported by the Academy of Finland (project grants 104781, 120315 and Center of Excellence in Complex Disease Genetics), University Hospital Oulu, Biocenter, University of Oulu, Finland, the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), the ENGAGE project and grant agreement HEALTH-F4-2007-201413, and the MRC (studentship grant G0500539). The NFBC authors thank P. Rantakallio for the launch of NFBC1966 and initial data collection, S. Vaara for data collection, T. Ylitalo for administration, M. Koiranen for data management, and O. Tornwall and M. Jussila for DNA biobanking.

Author Contributions A.I.F.B., P.F., J.S.B. and L.J.M.C. designed and supervised the study. F.C., D.M., S.J., J.A. and S.B. coordinated and managed patient databases. R.G.W., A.V., A.J.d.S., C.L., F.S., F.C., J.-C.C., J.L.B., S.L., N.H. and J.S.E.-S.M. performed data analysis. A.J.d.S. conducted the MLPA analysis. J.A., M.F. and A.J.W. analysed expression data. A.-E.A., A.B., A.D., A.F., A.G., A.G., A.L., A.P., B.B., B.D., B.I., B.L., C.V.-D., C.L.C., D.C., D.M., D.S., F.F., G.M., G.P., J.-L.M., J.-M.C., J.A., J.C., K.M., K.D.M., K.O., M.M.v.H., M.-P.C., M.-P.L., M.P., M.B.-D., M.H.-E., M.M., N.C., O.B., P.J., R.C., R.E., R.F.K., R.T., S.D.-G., S.J., V.G. and V.M. supervised patient recruitment and performed cytogenetic analysis. A.-L.H., A.K., A.M., A.R., B.B., D.M., D.W., E.G.B., E.H., F.P., G.W., I.S.F., J.A., J.K., L.C., L.P., L.S., M.E.H., M.I.M., M.N., M.-R.J., N.H., P.E., P.J., P.P., P.V., R.S., S.B., S.O’R., T.E., V.M. and V.V. supervised cohort recruitment and/or conducted genotyping. R.G.W., S.J., A.V., A.J.d.S., L.J.M.C., A.I.F.B., P.F. and J.S.B. wrote and edited the manuscript and prepared figures. P.F. and J.S.B. contributed equally. All authors commented on and approved the manuscript.

Author information

Author notes

1. M. M. van Haelst
   Present address: †Present address: Department of Medical Genetics, University Medical Centre Utrecht, 3584 EA Utrecht, The Netherlands.,
2. R. G. Walters and S. Jacquemont: *These authors contributed equally to this work.

Authors and Affiliations

1. Section of Genomic Medicine, Imperial College London, London W12 0NN, UK.,
   R. G. Walters, A. J. de Smith, J. Andersson, M. Falchi, J. S. El-Sayed Moustafa, J. L. Buxton, A. J. Walley, A. I. F. Blakemore & P. Froguel
2. Department of Epidemiology and Public Health, Imperial College London, London W2 1PG, UK.,
   R. G. Walters, P. Elliott, M.-R. Jarvelin & L. J. M. Coin
3. Service de Génétique Médicale, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.,
   S. Jacquemont, D. Martinet, M. Gaillard, F. Fellmann, A. Ferrarini & J. S. Beckmann
4. Departement de Génétique Médicale, Université de Lausanne, CH-1015 Lausanne, Switzerland.,
   A. Valsesia, S. Bergmann & J. S. Beckmann
5. Ludwig Institute for Cancer Research, Université de Lausanne, CH-1015 Lausanne, Switzerland.,
   A. Valsesia
6. Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.,
   A. Valsesia & S. Bergmann
7. Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.,
   F. Chen & N. Hadjikhani
8. Laboratoire de Génétique Médicale, Centre Hospitalier Régional Universitaire, 59000 Lille, France.,
   J. Andrieux & S. Bouquillon
9. CNRS 8090-Institute of Biology, Pasteur Institute, 59800 Lille, France.,
   S. Lobbens, F. Stutzmann, J.-C. Chèvre, C. Lecoeur, V. Vatin, D. Meyre & P. Froguel
10. Centre de Génétique Chromosomique, Hôpital Saint-Vincent de Paul, GHICL, 59020 Lille, France.,
    B. Delobel
11. Service de Génétique Clinique, Hôpital Jeanne de Flandre, Centre Hospitalier Universitaire de Lille, 59000 Lille, France.,
    O. Boute & M. Holder-Espinasse
12. Service de Neuropédiatrie, Centre Hospitalier Régional Universitaire, 59000 Lille, France.,
    J.-M. Cuisset & M.-P. Lemaitre
13. Unité Multidisciplinaire de Santé des Adolescents, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.,
    A.-E. Ambresin
14. Service de Neuropsychologie et de Neuroréhabilitation, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.,
    A. Brioschi
15. Service d’Endocrinologie, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.,
    V. Giusti
16. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.,
    N. Hadjikhani
17. INSERM, U614, Faculté de Médecine, 76183 Rouen, France.,
    D. Campion & A. Guilmatre
18. Service de Génétique, Centre Hospitalier Universitaire de Rouen, 76031 Rouen, France.,
    A. Goldenberg
19. Laboratoire de Diagnostic Génétique, Nouvel Hôpital civil, 67091 Strasbourg, France.,
    N. Calmels & J.-L. Mandel
20. Centre Hospitalier Universitaire Nantes, Service de Génétique Médicale, 44093 Nantes, France.,
    C. Le Caignec, A. David & B. Isidor
21. INSERM, UMR915, L’Institut du Thorax, 44007 Nantes, France.,
    C. Le Caignec
22. Service de Génétique, Hospices Civils de Lyon, Hôpital de l’Hotel Dieu, 69288 Lyon, France.,
    M.-P. Cordier, S. Dupuis-Girod, A. Labalme & D. Sanlaville
23. EA 4171, Université Claude Bernard, 69622 Lyon, France.,
    D. Sanlaville
24. Laboratoire de Génétique, Centre Hospitalier Universitaire, Nancy Université, 54511 Vandoeuvre les Nancy, France.,
    M. Béri-Dexheimer, P. Jonveaux & B. Leheup
25. EA4368 Medical School Nancy, Université Henri Poincaré, 54003 Nancy, France.,
    B. Leheup
26. Department of Genetics, United Laboratories, Tartu University Children’s Hospital, 50406 Tartu, Estonia.,
    K. Õunap
27. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK.,
    E. G. Bochukova, E. Henning, J. Keogh, S. O’Rahilly & I. S. Farooqi
28. North West Thames Regional Genetics Service, Northwick Park & St Marks Hospital, Harrow HA1 3UJ, UK.,
    R. J. Ellis, K. D. MacDermot & M. M. van Haelst
29. Centre Hospitalier D’Arras, Génétique Médicale, 62000 Arras, France.,
    C. Vincent-Delorme
30. Service de Génétique Médicale, Centre Hospitalier Universitaire Clemenceau, 14033 Caen, France.,
    G. Plessis
31. Centre Hospitalier Universitaire–Hôpital Nord, Service de Génétique, 42055 Saint Étienne, France.,
    R. Touraine
32. Département de Génétique et INSERM U781, Université Paris Descartes, Hôpital Necker-Enfants Malades, 75015 Paris, France.,
    A. Philippe & V. Malan
33. Service de Génétique Clinique, Centre Hospitalier Universitaire, 80054 Amiens, France.,
    M. Mathieu-Dramard
34. Laboratoire de Cytogénétique, Centre Hospitalier Universitaire Caremeau, 30029 Nîmes, France.,
    J. Chiesa
35. Department of Medical Genetics, University Hospital & University of Antwerp, 2650 Edegem, Belgium.,
    B. Blaumeiser & R. F. Kooy
36. INSERM U859, Biotherapies for Diabetes, 59045 Lille, France.,
    R. Caiazzo & F. Pattou
37. Université Lille Nord de France, Centre Hospitalier Universitaire Lille, 59037 Lille, France.,
    R. Caiazzo, M. Pigeyre & F. Pattou
38. INSERM U780-IFR69, 94807 Villejuif, France.,
    B. Balkau
39. McGill University and Genome Quebec Innovation Centre, Montreal H3A 1A4, Canada.,
    R. Sladek
40. Department of Medicine and Human Genetics, McGill University, Montreal H3A 1B1, Canada.,
    R. Sladek
41. Division of Genetics, GlaxoSmithKline, Philadelphia, Pennsylvania 19101, USA.,
    V. Mooser & D. Waterworth
42. The Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.,
    A. Reymond
43. Department of Medicine, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.,
    P. Vollenweider & G. Waeber
44. Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.,
    A. Kurg, P. Palta & K. Männik
45. Estonian Genome Project, University of Tartu, 50410 Tartu, Estonia.,
    T. Esko, A. Metspalu & M. Nelis
46. Estonian Biocentre, 51010 Tartu, Estonia.,
    T. Esko, A. Metspalu & M. Nelis
47. Department of Obstetrics and Gynaecology, University of Oulu, 90220 Oulu, Finland.,
    A.-L. Hartikainen
48. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK.,
    M. I. McCarthy
49. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.,
    M. I. McCarthy
50. Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.,
    L. Peltonen, N. Huang & M. E. Hurles
51. Institute of Molecular Medicine, Biomedicum, 00290 Helsinki, Finland.,
    L. Peltonen
52. Massachusetts Institute of Technology, The Broad Institute, Cambridge, Massachusetts 02142, USA.,
    L. Peltonen
53. Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, The Sahlgrenska Academy, 413 45 Göteborg, Sweden.,
    L. Carlsson, P. Jacobson & L. Sjöström
54. Department of Child and Adolescent Health, National Public Health Institute, 90101 Oulu, Finland.,
    M.-R. Jarvelin
55. Institute of Health Sciences and Biocenter Oulu, University of Oulu, 90220 Oulu, Finland.,
    M.-R. Jarvelin

Authors

1. R. G. Walters
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2. S. Jacquemont
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3. A. Valsesia
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4. A. J. de Smith
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5. D. Martinet
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6. J. Andersson
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7. M. Falchi
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8. F. Chen
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9. J. Andrieux
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10. S. Lobbens
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11. B. Delobel
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12. F. Stutzmann
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13. J. S. El-Sayed Moustafa
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14. J.-C. Chèvre
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15. C. Lecoeur
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16. V. Vatin
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17. S. Bouquillon
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18. J. L. Buxton
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19. O. Boute
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20. M. Holder-Espinasse
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21. J.-M. Cuisset
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22. M.-P. Lemaitre
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23. A.-E. Ambresin
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24. A. Brioschi
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25. M. Gaillard
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26. V. Giusti
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27. F. Fellmann
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28. A. Ferrarini
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29. N. Hadjikhani
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30. D. Campion
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31. A. Guilmatre
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32. A. Goldenberg
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33. N. Calmels
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34. J.-L. Mandel
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35. C. Le Caignec
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36. A. David
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37. B. Isidor
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38. M.-P. Cordier
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39. S. Dupuis-Girod
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40. A. Labalme
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41. D. Sanlaville
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42. M. Béri-Dexheimer
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43. P. Jonveaux
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44. B. Leheup
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45. K. Õunap
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46. E. G. Bochukova
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47. E. Henning
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48. J. Keogh
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49. R. J. Ellis
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50. K. D. MacDermot
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51. M. M. van Haelst
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52. C. Vincent-Delorme
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53. G. Plessis
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54. R. Touraine
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55. A. Philippe
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56. V. Malan
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57. M. Mathieu-Dramard
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58. J. Chiesa
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59. B. Blaumeiser
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60. R. F. Kooy
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61. R. Caiazzo
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62. M. Pigeyre
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63. B. Balkau
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Corresponding authors

Correspondence toP. Froguel or J. S. Beckmann.

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Walters, R., Jacquemont, S., Valsesia, A. et al. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.Nature 463, 671–675 (2010). https://doi.org/10.1038/nature08727

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• Received: 16 November 2009
• Accepted: 01 December 2009
• Issue Date: 04 February 2010
• DOI: https://doi.org/10.1038/nature08727