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Abstract

We analyzed genome-wide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls. Thirty-eight markers showing strong association were further evaluated in 14,186 European subjects. In addition to FTO and MC4R, we detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene, P = 2.9 × 10−7), near MAF (encoding the transcription factor c-MAF, P = 3.8 × 10−13) and near PTER (phosphotriesterase-related gene, P = 2.1 × 10−7).

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Acknowledgements

We thank the subjects and families who participated in this study. This work was supported by grants from the “Agence Nationale de la Recherche,” the “Conseil Regional Nord-Pas de Calais/Fonds européen de développement économique et régional,” Genome Quebec/Genome Canada and the Medical Research Council. The German cohorts and projects were supported by grants from the German Research Council (KFO152 “Atherobesity”). We thank F. Allegaert, M. Deweirder, R. Tauscher and A. Berthold for their technical support in DNA extraction and distribution. We thank P. Bougnères and C. Le Stunff for providing DNA samples of the “Saint Vincent de Paul” obese children cohort. Northern Finland Birth Cohort 1986 (NFBC1986) was supported by the European Commission; contract number QLG1-CT-2000-01643, Biocenter, University of Oulu, Finland and the Academy of Finland. We thank L. Peltonen for providing NFBC1986 DNA samples. We acknowledge the “Centre de Médecine Préventive (CMP) de Vandoeuvre les Nancy” where the STANISLAS cohort was recruited.

Author information

Affiliations

  1. CNRS 8090-Institute of Biology, Pasteur Institute, 59000 Lille, France.

    • David Meyre
    • , Jérôme Delplanque
    • , Jean-Claude Chèvre
    • , Cécile Lecoeur
    • , Stéphane Lobbens
    • , Sophie Gallina
    • , Emmanuelle Durand
    • , Vincent Vatin
    • , Franck Degraeve
    • , Christine Proença
    • , Stefan Gaget
    • , Christian Dina
    •  & Philippe Froguel
  2. University Hospital for Children & Adolescents, University of Leipzig, 04103 Leipzig, Germany.

    • Antje Körner
    •  & Wieland Kiess
  3. Interdisciplinary Centre for Clinical Research, University of Leipzig, 04103 Leipzig, Germany.

    • Peter Kovacs
  4. Institut Inter Régional pour la Santé, 37521 La Riche, France.

    • Jean Tichet
  5. Department of Endocrinology, Diabetology, Nutrition, Bichat-Claude Bernard University Hospital, Assistance Publique des Hôpitaux de Paris, 75018 Paris, France, and Institut National de la Santé et de la Recherche Médicale U695, Université Paris 7, 75007 Paris, France.

    • Michel Marre
  6. Department of Clinical Sciences/ Obstetrics and Gynecology, University of Oulu, University of Oulu, 90014 Oulu, Finland.

    • Anna-Liisa Hartikainen
  7. Klinik Lindberg, 8400 Winterthur, and University of Berne, 3012 Berne, Switzerland.

    • Fritz Horber
    •  & Natascha Potoczna
  8. Unité Mixte de Recherche U557 Institut National de la Santé et de la Recherche Médicale, U1125 Institut National de la Recherche Agronomique, Conservatoire National des arts et Métiers, Université Paris 13, Centre de Recherches en Nutrition Humaine Ile de France, F-93017 Bobigny, France.

    • Serge Hercberg
  9. Institut National de la Santé et de la Recherche Médicale, U690, Paris, FR-75019, France and Université Paris Diderot, Paris, FR-75205 cedex 13, France.

    • Claire Levy-Marchal
  10. Institut National de la Santé et de la Recherche Médicale U859, Centre Hospitalier Régional Universitaire de Lille, Lille North of France University, 59000 Lille France.

    • François Pattou
  11. Institut National de la Santé et de la Recherche Médicale U780, Villejuif, F-94807; University Paris-Sud, Orsay, F-91405, France.

    • Barbara Heude
    •  & Beverley Balkau
  12. Institut National de la Santé et de la Recherche Médicale U563, Children's Hospital, Centre Hospitalier Universitaire 31000 Toulouse, France.

    • Maithé Tauber
  13. Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, OX3 7LJ Oxford, UK.

    • Mark I McCarthy
  14. Wellcome Trust Centre for Human Genetics, University of Oxford, OX3 Oxford, UK.

    • Mark I McCarthy
  15. Oxford National Institute for Health Research Biomedical Research Centre, OX3 Oxford, UK.

    • Mark I McCarthy
  16. Section of Genomic Medicine, Hammersmith Hospital, Imperial College London, W12 0HS London, UK.

    • Alexandra I F Blakemore
    • , Julian Asher
    • , Andrew Walley
    •  & Philippe Froguel
  17. McGill University and Genome Quebec Innovation Centre, H3A 1A Montreal, Canada.

    • Alexandre Montpetit
    • , Constantin Polychronakos
    •  & Rob Sladek
  18. Pediatric Endocrine Unit, Jeanne de Flandre Hospital, 59000 Lille, France.

    • Jacques Weill
  19. Department of Epidemiology and Public Health, Imperial College London, WC1E 6BT London UK.

    • Lachlan J M Coin
    • , Paul Elliott
    • , Marjo-Riitta Järvelin
    •  & David Balding
  20. Institute of Health Sciences, University of Oulu, Department of Child and Adolescent Health, National Public Health Institute, Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.

    • Marjo-Riitta Järvelin
  21. Institut National de la Santé et de la Recherche Médicale “Cardiovascular Genetics” team, Centre D'investigation Clinique 54000 Nancy, France.

    • Sophie Visvikis-Siest

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Contributions

Writing team: D.M., P.F., J.-C.C., A.I.F.B., M.I.M., A.W., C.D., R.S.; all others reviewed and approved the manuscript. Project management: D.M., J.D., A.W., C.D., P.F. Genome-wide association sampling and genotyping: D.M., J.D., S.L., E.D., J.T., M.M., M.T., S.V.-S., R.S., B.H., A.M., C.P., B.B. Confirmation study sampling and genotyping: D.M., J.D., E.D., V.V., A.K., P.K., W.K., J.T., M.M., A.L.H., P.E., F.H., N.P., S.H., C.L-.M., F.P., B.H., J.W., M.-R.J., B.B. Statistical analysis and informatics: D.M., C.L., S.G., F.D., C.P., S.G., L.J.M.C., J.A., D.B., C.D. Candidate gene analysis: J.C.C., D.M., S.G., F.D., S.G.

Corresponding author

Correspondence to Philippe Froguel.

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    Supplementary Text and Figures

    Supplementary Figures 1 and 2, Supplementary Tables 1–4 and Supplementary Methods

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DOI

https://doi.org/10.1038/ng.301

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