Common variants near MC4R are associated with fat mass, weight and risk of obesity (original) (raw)

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Acknowledgements

We acknowledge support of the UK Medical Research Council, the Wellcome Trust, Diabetes UK, Cancer Research United Kingdom, BDA Research, UK National Health Service Research and Development, the European Commission, the Academy of Finland, the British Heart Foundation, the National Institutes of Health, the Novartis Institutes for BioMedical Research, GlaxoSmithKline and the German National Genome Research Net. Personal support was provided by NIDDK (E.K.S., H.N.L., J.N.H., F.S.C.), the Wellcome Trust (A.T.H., E.Z.), Diabetes UK (R.M.F.), the Throne-Holst Foundation (C.M.L.), the Vandervell Foundation (M.N.W.), American Diabetes Association (C.J.W.), Unilever Corporate Research (S.L.) and the British Heart foundation (N.J.S).

Author information

Author notes

1. Ruth J F Loos, Cecilia M Lindgren, Shengxu Li, Mark I McCarthy, Nicholas J Wareham and Inês Barroso: These authors contributed equally to this work.
2. Department of Public Health, University of Helsinki, 00014 Helsinki, Finland.

Authors and Affiliations

1. MRC Epidemiology Unit, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
   Ruth J F Loos, Shengxu Li, Jing Hua Zhao, Ken K Ong, Manjinder S Sandhu, Matthew A Sims & Nicholas J Wareham
2. Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
   Ruth J F Loos, Shengxu Li, Jing Hua Zhao, I Sadaf Farooqi, Ken K Ong, Stephen O'Rahilly, Matthew A Sims, Vicki L Wraight & Nicholas J Wareham
3. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
   Cecilia M Lindgren, Inga Prokopenko, Amanda J Bennett, Katherine S Elliott, David M Evans, Christopher J Groves, Blanca Herrera, Joshua C Randall, Nigel W Rayner, Nicholas J Timpson, Eleftheria Zeggini & Mark I McCarthy
4. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK
   Cecilia M Lindgren, Inga Prokopenko, Amanda J Bennett, Christopher J Groves, Blanca Herrera, Fredrik Karpe, Matthew J Neville, Katharine R Owen, Joshua C Randall, Nigel W Rayner & Mark I McCarthy
5. Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK
   Eleanor Wheeler, Michael Inouye, Antony P Attwood, Emmanouil T Dermitzakis, Jilur Ghori, Rhian Gwilliam, Sarah E Hunt, Andrew Keniry, Ralph McGinnis, Alexandra C Nica, Simon Potter, Nicole Soranzo, Panos Deloukas & Inês Barroso
6. Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, EX1 2LU, UK
   Rachel M Freathy, Andrew T Hattersley, Michael N Weedon & Timothy M Frayling
7. Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK
   Rachel M Freathy, Andrew T Hattersley, Michael N Weedon & Timothy M Frayling
8. Department of Haematology, University of Cambridge, and NHS (National Health Service) Blood and Transplant, Cambridge Centre, Long Road, Cambridge, UK
   Antony P Attwood, Jennifer D M Jolley & Willem H Ouwehand
9. Department of Medical Genetics, University of Lausanne, 1011, Switzerland
   Jacques S Beckmann, Sven Bergmann & Toby Johnson
10. Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, 1011, Switzerland
    Jacques S Beckmann
11. Division of Cancer Epidemiology and Genetics, Department of Health and Human Services (DHHS), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland
    Sonja I Berndt, Stephen J Chanock & Richard B Hayes
12. Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland
    Sven Bergmann & Toby Johnson
13. MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Cambridge, CB2 0XY, UK
    Sheila A Bingham
14. University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, 1011, Switzerland
    Murielle Bochud & Toby Johnson
15. Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
    Morris Brown
16. CNRS-8090-Institute of Biology, Pasteur Institute, Lille, 5900, France
    Stéphane Cauchi, Christian Dina, Philippe Froguel & David Meyre
17. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, G12 8TA, UK
    John M Connell
18. MRC Epidemiology Resource Centre, University of Southampton, Southampton, SO16 6YD, UK
    Cyrus Cooper, Ian Day & Holly E Syddall
19. The MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, BS8 2PR, UK
    George Davey Smith, David M Evans & Nicholas J Timpson
20. MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, UK
    Subhajyoti De & Sarah A Teichmann
21. Division of Medicine and Therapeutics, Diabetes Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
    Alex S F Doney & Andrew D Morris
22. Department of Epidemiology and Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK
    Paul Elliott & Marjo-Riitta Jarvelin
23. Department of Public Health Science and General Practice, Fin-90014, University of Oulu, Finland
    Paul Elliott & Marjo-Riitta Jarvelin
24. Metabolic Research Laboratories, University of Cambridge, Cambridge, CB2 0QQ, UK
    I Sadaf Farooqi, Stephen O'Rahilly & Vicki L Wraight
25. Genomic Medicine, Hammersmith Hospital, Imperial College London, London, W12 ONN, UK
    Philippe Froguel
26. Division of Community Health Sciences, St George's, University of London, London, SW17 0RE, UK
    David Hadley, Konstantinos Papadakis & David P Strachan
27. LIGHT Research Institutes, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK
    Alistair S Hall
28. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, D45147, Germany
    Johannes Hebebrand, Anke Hinney & Carla I Ganz Vogel
29. GSF-Institute of Epidemiology, Neuherberg-Munich, D-85764, Germany
    Iris M Heid, Claudia Lamina, Christian Gieger, Thomas Illig & H-Erich Wichmann
30. IBE Chair of Epidemiology, University of Munich, Munich, D-81377, Germany
    Iris M Heid, Christian Gieger & H-Erich Wichmann
31. Department of Child and Adolescent Health, National Public Health Institute, Oulu, 90221, Finland
    Marjo-Riitta Jarvelin & Anneli Pouta
32. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, CB2 2SR, UK
    Kay-Tee Khaw, Robert N Luben & Manjinder S Sandhu
33. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK
    Massimo Mangino & Nilesh J Samani
34. Department of Statistics, University of Oxford, 1 South Parks Road, Oxford, OX1 3TG, UK
    Jonathan Marchini
35. Department of Social Medicine, University of Bristol,
    Wendy L McArdle & Susan M Ring
36. Canynge Hall, Whiteladies Road, Bristol, BS8 2PR, UK
    Wendy L McArdle & Susan M Ring
37. Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine, Charterhouse Square, London, EC1M 6BQ, UK
    Patricia B Munroe, Chris Wallace & Mark J Caulfield
38. Department of Oral and Dental Science, Bristol Dental School, University of Bristol, Lower Maudlin Street, Bristol, BS1 2LY, UK
    Andrew R Ness
39. Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK
    Colin N A Palmer
40. Department of Obstetrics and Gynaecology, University Hospital of Oulu, P.P. Box 22, Oulu, 90221, Finland
    Anneli Pouta
41. Department of Nutrition, Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Lu Qi, David J Hunter & Frank B Hu
42. Institute of Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, 45122, Germany
    André Scherag
43. Medical Genetics/Clinical Pharmacology and Discovery Medicine, King of Prussia, 19406, Pennsylvania, USA
    Kijoung Song, Dawn M Waterworth, Xin Yuan & Vincent Mooser
44. Department of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, USA
    Elizabeth K Speliotes
45. Broad Institute at MIT and Harvard, Boston, 02115, Massachusetts, USA
    David J Hunter, Elizabeth K Speliotes, Helen N Lyon, Benjamin F Voight & Joel N Hirschhorn
46. Clinical Science at South Bristol, University of Bristol, Bristol, BS2 8AE, UK
    Jonathan H Tobias
47. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, 09100, Italy
    Manuela Uda, Serena Sanna & Giuseppe Albai
48. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Cristen J Willer, Anne U Jackson & Michael Boehnke
49. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Helen N Lyon & Joel N Hirschhorn
50. Division of Genetics, Children's Hospital, Boston, 02115, Massachusetts, USA
    Joel N Hirschhorn
51. Department of Pediatrics, Harvard Medical School, Boston, 02115, Massachusetts, USA
    Helen N Lyon & Joel N Hirschhorn
52. Division of Endocrinology, Children's Hospital, Boston, 02115, Massachusetts, USA
    Joel N Hirschhorn
53. Department of Medicine and Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, 1011, Switzerland
    Peter Vollenweider & Gerard Waeber
54. Bioinformed Consulting Services, Gaithersburg, 20877, Maryland, USA
    Kevin B Jacobs
55. Pediatric Oncology Branch, Center for Cancer Research, NCI, NIH, DHHS, Bethesda, 20892, Maryland, USA
    Stephen J Chanock
56. GSF-Institute of Human Genetics, Neuherberg-Munich, D-85764, Germany
    Thomas Meitinger
57. Institute of Human Genetics, Technical University Munich, Munich, D-81671, Germany
    Thomas Meitinger
58. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, 02115, Massachusetts, USA
    Peter Kraft & David J Hunter
59. Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Boston, 02115, Massachusetts, USA
    Susan E Hankinson, David J Hunter & Frank B Hu
60. Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
    Benjamin F Voight
61. Department of Medicine, Massachusetts General Hospital and Harvard Medical School Boston, 02114, Massachusetts, USA
    Benjamin F Voight
62. Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
    Benjamin F Voight
63. Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, Malmö, S-205 02, Sweden
    Martin Ridderstrale & Leif Groop
64. Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, 00029, Finland
    Leif Groop
65. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, Michigan, USA
    Paul Scheet & Goncalo R Abecasis
66. Gerontology Research Center, National Institute on Aging, Baltimore, 21244, Maryland, USA
    Ramaiah Nagaraja & David Schlessinger
67. Department of Epidemiology and Health Promotion, Diabetes Unit, National Public Health Institute, Helsinki, 00300, Finland
    Jaakko Tuomilehto & Jaakko Tuomilehto
68. South Ostrobothnia Central Hospital, Seinäjoki, 60220, Finland
    Jaakko Tuomilehto
69. Genome Technology Branch, National Human Genome Research Institute, Bethesda, 20892, Maryland, USA
    Francis S Collins
70. Department of Genetics, University of North Carolina, Chapel Hill, 27599, North Carolina, USA
    Karen L Mohlke

Authors

1. Ruth J F Loos
2. Cecilia M Lindgren
3. Shengxu Li
4. Eleanor Wheeler
5. Jing Hua Zhao
6. Inga Prokopenko
7. Michael Inouye
8. Rachel M Freathy
9. Antony P Attwood
10. Jacques S Beckmann
11. Sonja I Berndt
12. Sven Bergmann
13. Amanda J Bennett
14. Sheila A Bingham
15. Murielle Bochud
16. Morris Brown
17. Stéphane Cauchi
18. John M Connell
19. Cyrus Cooper
20. George Davey Smith
21. Ian Day
22. Christian Dina
23. Subhajyoti De
24. Emmanouil T Dermitzakis
25. Alex S F Doney
26. Katherine S Elliott
27. Paul Elliott
28. David M Evans
29. I Sadaf Farooqi
30. Philippe Froguel
31. Jilur Ghori
32. Christopher J Groves
33. Rhian Gwilliam
34. David Hadley
35. Alistair S Hall
36. Andrew T Hattersley
37. Johannes Hebebrand
38. Iris M Heid
39. Blanca Herrera
40. Anke Hinney
41. Sarah E Hunt
42. Marjo-Riitta Jarvelin
43. Toby Johnson
44. Jennifer D M Jolley
45. Fredrik Karpe
46. Andrew Keniry
47. Kay-Tee Khaw
48. Robert N Luben
49. Massimo Mangino
50. Jonathan Marchini
51. Wendy L McArdle
52. Ralph McGinnis
53. David Meyre
54. Patricia B Munroe
55. Andrew D Morris
56. Andrew R Ness
57. Matthew J Neville
58. Alexandra C Nica
59. Ken K Ong
60. Stephen O'Rahilly
61. Katharine R Owen
62. Colin N A Palmer
63. Konstantinos Papadakis
64. Simon Potter
65. Anneli Pouta
66. Lu Qi
67. Joshua C Randall
68. Nigel W Rayner
69. Susan M Ring
70. Manjinder S Sandhu
71. André Scherag
72. Matthew A Sims
73. Kijoung Song
74. Nicole Soranzo
75. Elizabeth K Speliotes
76. Holly E Syddall
77. Sarah A Teichmann
78. Nicholas J Timpson
79. Jonathan H Tobias
80. Manuela Uda
81. Carla I Ganz Vogel
82. Chris Wallace
83. Dawn M Waterworth
84. Michael N Weedon
85. Cristen J Willer
86. Vicki L Wraight
87. Xin Yuan
88. Eleftheria Zeggini
89. Joel N Hirschhorn
90. David P Strachan
91. Willem H Ouwehand
92. Mark J Caulfield
93. Nilesh J Samani
94. Timothy M Frayling
95. Peter Vollenweider
96. Gerard Waeber
97. Vincent Mooser
98. Panos Deloukas
99. Mark I McCarthy
100. Nicholas J Wareham
101. Inês Barroso

Consortia

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

• Kevin B Jacobs
• , Stephen J Chanock
• & Richard B Hayes

KORA

• Claudia Lamina
• , Christian Gieger
• , Thomas Illig
• , Thomas Meitinger
• & H-Erich Wichmann

Nurses' Health Study

• Peter Kraft
• , Susan E Hankinson
• , David J Hunter
• & Frank B Hu

Diabetes Genetics Initiative

• Helen N Lyon
• , Benjamin F Voight
• , Martin Ridderstrale
• & Leif Groop

The SardiNIA Study

• Paul Scheet
• , Serena Sanna
• , Goncalo R Abecasis
• , Giuseppe Albai
• , Ramaiah Nagaraja
• & David Schlessinger

The Wellcome Trust Case Control Consortium

FUSION

• Anne U Jackson
• , Jaakko Tuomilehto
• , Francis S Collins
• , Michael Boehnke
• & Karen L Mohlke

Contributions

Writing team: R.J.F.L., C.M.L., S.L., M.I.M., N.J.W., I.B.

Project management: R.J.F.L., C.M.L., P.D., M.I.M., N.J.W., I.B.

Genome-wide association sampling, genotyping and analysis: R.J.F.L., C.M.L., S.L., E.W., J.H.Z., I.P., M.I., A.P.A., J.S.B., S.B., S.A.B., M. Bochud, M. Brown, J.M.C., D.M.E., J.G., R.G., D.H., A.S.H., A.T.H., S.E.H., T.J., J.D.M.J., A.K., K.-T.K., R.L., M.M., J.M., W.L.M., R.M., P.B.M., A.C.N., K.K.O., K.P., S.P., S.M.R., M.S.S., M.A.S., K.S., N.S., N.J.T., C.W., D.M.W., M.N.W., The Wellcome Trust Case Control Consortium, X.Y., E.Z., D.P.S., W.H.O., M.J.C., N.J.S., T.M.F., P.V., G.W., V.M., P.D., M.I.M., N.J.W., I.B., A.J.B.

Replication samples, genotyping and analysis in adults: R.J.F.L., C.M.L., S.L., R.M.F., A.P.A., A.B., S.C., C.C., G.D.S., I.D., C.D., A.S.F.D., P.E., D.M.E., P.F., C.J.G., A.T.H., M.-R.J., J.D.M.J., F.K., D.M., A.D.M., M.J.N., K.K.O., S.O., K.R.O., C.N.A.P., A.P., A.R.N., S.M.R., M.S.S., M.A.S., H.E.S., N.J.T., M.N.W., V.L.W., E.Z., W.H.O., T.M.F., M.I.M., N.J.W., I.B.

GIANT Consortium samples, genotyping and analysis: S.I.B., K.B.J., S.J.C., R.B.H., I.M.H., C.L., C.G., T.I., T.M., H.-E.W., L.Q., P K., S.E.H., D.J.H., F.B.H, E.K.S., H.N.L., B.F.V., M.R., L.G., J.N.H., M.U., P.S., S.S., G.R.A., G.A., R.N., D.S., C.J.W., A.U. J., J.T., F.S.C., M. Boehnke., K.L.M., FUSION, DGI, PLCO, NHS, SardiNIA.

Replication samples, analysis and genotyping in children: R.M.F., S.C., G.D.S., I.D., C.D., I.S.F., P.F., A.T.H., J.H., A.H., D.M., A.R.N., K.K.O., S.O., S.M.R., A.S., N.J.T., J.H.T., V.L.W., T.M.F., C.I.G.V.

Statistical analysis and informatics: R.J.F.L., C.M.L., S.L., J.H.Z., I.P., R.M.F., S.D., E.T.D., K.S.E., B.H., S.E.H., T.J., J.M., R.M., S.P., J.C.R., N.W.R., A.S., S.A.T., N.J.T., E.Z., M.I.M., N.J.W., I.B.

Corresponding authors

Correspondence toMark I McCarthy, Nicholas J Wareham or Inês Barroso.

Ethics declarations

Competing interests

Vincent Mooser, Dawn Waterworth and Kijoung Song are full-time employees of GlaxoSmithKline.

Peter Vollenweider and Gérard Waeber received financial support from GlaxoSmithKline to build the CoLaus study.

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A full list of authors is provided in the Supplementary Note.

A full list of authors is provided at the end of the reference list.

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Loos, R., Lindgren, C., Li, S. et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity.Nat Genet 40, 768–775 (2008). https://doi.org/10.1038/ng.140

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• Received: 16 November 2007
• Accepted: 19 February 2008
• Published: 04 May 2008
• Issue Date: June 2008
• DOI: https://doi.org/10.1038/ng.140