Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile (original) (raw)

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Acknowledgements

A full list of Acknowledgments appears in the Supplementary Note. Funding was provided by Academy of Finland (10404, 124243, 129680, 129494, 141005 and 213506); Agency for Health Care Policy Research (HS06516); Althingi (the Icelandic Parliament); American Heart Association (10SDG269004); AstraZeneca; Baltimore Geriatric Research Education and Clinical Centers; Biocentrum Helsinki Foundation; Biotechnology and Biological Sciences Research Council (G20234); British Heart Foundation (PG/07/133/24260, RG/08/008, SP/04/002, SP/07/007/23671); CamStrad; Cancer Research UK; Cedars-Sinai Board of Governors' Chair in Medical Genetics; Centre for Medical Systems Biology (The Netherlands); Centre Hospitalier Universitaire Vaudois (Lausanne); Croatian Ministry of Science, Education and Sport (196-1962766-2747, 216-1080315-0302 and 309-0061194-2023); Department of Health (UK); Department of Veterans Affairs (USA); Emil and Vera Cornell Foundation; Erasmus Medical Center (Rotterdam); Erasmus University (Rotterdam); European Commission (DG XII, FP7/2007-2013, FP7-KBBE-2010-4-266408, HEALTH-F2-2007-201681, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2003-503041, LSHM-CT-2004-512013, QLG1-CT-2001-01252 and QLG2-CT-2002-01254); Finnish Diabetes Foundation; Finnish Diabetes Research Foundation; Finnish Foundation for Cardiovascular Research; Finnish Heart Foundation; Finnish Medical Society; Folkhälsan Research Foundation; Food Standards Agency (UK); Foundation for Life and Health in Finland; German Bündesministerium für Forschung und Technology (01AK803A-H and 01IG07015G); German Federal Ministry of Education and Research; German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Göteborg Medical Society; Gyllenberg Foundation; Health and Safety Executive (UK); Health Care Centers in Vasa, Närpes and Korsholm; Hjartavernd (the Icelandic Heart Association); John D. and Catherine T. MacArthur Foundation; Knut and Alice Wallenberg Foundation; Leenaards Foundation; Ludwig-Maximilians Universität München; Lundberg Foundation; Medical Research Council (UK); Men's Associates of Hebrew SeniorLife; Ministerio de Ciencia e Innovación (Spain) (SAF-2009 and SAF-2008-02073); Ministry for Health, Welfare and Sports (The Netherlands); Ministry of Education (Finland); Ministry of Education, Culture and Science (The Netherlands); Municipal Health Care Center and Hospital in Jakobstad; Municipality of Rotterdam; Närpes Health Care Foundation; National Institute for Health Research (UK); US National Institutes of Health (USA) (AG13196, DK063491, K23-DK080145, M01-RR00425, N01-AG12100, N01-AG62101, N01-AG62103, N01-AG62106, N01-HC15103, N01-HC25195, N01-HC35129, N01-HC45133, N01-HC55222, N01-HC75150, N01-HC85079 through N01-HC85086, P30-DK072488, R01-AG031890-01, R01-AG18728, R01-AG032098-01A1, R01-AR/AG41398, R01-AR046838, R01-DK06833603, R01-DK075787, R01-DK07568102, R01-HL036310-20A2, R01-HL087652, R01-HL08770003, R01-HL088119, U01-HL080295, U01-HL72515 and U01-HL84756); Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Organisation for Scientific Research (175.010.2005.011 and 911-03-012); Netherlands Organization for the Health Research and Development; Nordic Center of Excellence in Disease Genetics; Novo Nordisk Foundation; Ollqvist Foundation; Paavo Nurmi Foundation; Perklén Foundation; Petrus and Augusta Hedlunds Foundation; Research Institute for Diseases in the Elderly (014-93-015; RIDE2); Robert Dawson Evans Endowment; Royal Society (UK); Sahlgrenska Center for Cardiovascular and Metabolic Research (A305:188); Sahlgrenska University Hospital Foundation (ALF/LUA); Science Funding programme (UK); Scottish Executive Health Department; Sigrid Juselius Foundation; State of Bavaria; Stroke Association (UK); Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research; Swedish Research Council (K2010-54X-09894-19-3, K2010-52X-20229-05-3 and 2006-3832); Swedish Strategic Foundation; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 310000-112552 and 33CSCO-122661); TEKES (1510/31/06); Torsten and Ragnar Söderberg's Foundation; United Kingdom NIHR Cambridge Biomedical Research Centre; University of Lausanne; University of Maryland General Clinical Research Center (M01 RR 16500); Uppsala University; Västra Götaland Foundation; and Wellcome Trust (077016/Z/05/Z, 084723/Z/08/Z and 091746/Z/10/Z).

Author information

Author notes

  1. Leena Peltonen: Deceased.

Authors and Affiliations

  1. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK
    Tuomas O Kilpeläinen, Francis M Finucane, Claudia Langenberg, Jian'an Luan, Jing-Hua Zhao, Nicholas J Wareham & Ruth J F Loos
  2. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
    M Carola Zillikens, Karol Estrada, Leonie C Jacobs, André G Uitterlinden & Fernando Rivadeneira
  3. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
    M Carola Zillikens, Karol Estrada, Albert Hofman, André G Uitterlinden, Cornelia M van Duijn & Fernando Rivadeneira
  4. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
    Alena Stančákova, Johanna Kuusisto & Markku Laakso
  5. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
    Janina S Ried, Angela Döring, Christian Gieger, Norman Klopp, Brigitte Kühnel & H-Erich Wichmann
  6. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
    Weihua Zhang & John C Chambers
  7. Department of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
    Jacques S Beckmann
  8. Department of Internal Medicine, Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    Liesbeth Vandenput, Mattias Lorentzon, Dan Mellström & Claes Ohlsson
  9. deCODE Genetics, Reykjavik, Iceland
    Unnur Styrkarsdottir, Bjarni V Halldorsson, Gudmar Thorleifsson, Unnur Thorsteinsdottir & Kari Stefansson
  10. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
    Yanhua Zhou & L Adrienne Cupples
  11. Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Kopavogur, Iceland
    Albert Vernon Smith, Gudny Eiriksdottir & Vilmundur Gudnason
  12. Department of Epidemiology, Genetic Epidemiology Unit, Erasmus MC, Rotterdam, The Netherlands
    Najaf Amin, Yurii S Aulchenko, Ben A Oostra, Karol Estrada, Albert Hofman, André G Uitterlinden, Cornelia M van Duijn & Fernando Rivadeneira
  13. Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
    Sailaja Vedantam, Candace Guiducci, Joel N Hirschhorn & Elizabeth K Speliotes
  14. Divisions of Genetics and Endocrinology and Program in Genomics, Children's Hospital, Boston, Massachusetts, USA
    Sailaja Vedantam & Joel N Hirschhorn
  15. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
    So-Youn Shin, Leena Peltonen, Inês Barroso & Nicole Soranzo
  16. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
    Talin Haritunians
  17. Division of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Mao Fu, Braxton D Mitchell, Jeffery R O'Connell & Alan R Shuldiner
  18. Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, USA
    Mary F Feitosa & Ingrid B Borecki
  19. Department of Epidemiology, Genetic Epidemiology Group, University College London, London, UK
    Meena Kumari
  20. Reykjavik University, Reykjavik, Iceland
    Bjarni V Halldorsson
  21. Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
    Emmi Tikkanen, Leena Peltonen, Markus Perola & Samuli Ripatti
  22. Public Health Genomics, National Institute for Health and Welfare, Helsinki, Finland
    Emmi Tikkanen, Leena Peltonen, Markus Perola & Samuli Ripatti
  23. King's College London, London, UK
    Massimo Mangino & Timothy D Spector
  24. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, UK
    Caroline Hayward & Alan F Wright
  25. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Ci Song & Erik Ingelsson
  26. Department of Biostatistics, University of Washington, Seattle, Washington, USA
    Alice M Arnold & Barbara McKnight
  27. Centre for Population Health Sciences, The University of Edinburgh Medical School, Edinburgh, UK
    Harry Campbell, Sarah H Wild, James F Wilson & Igor Rudan
  28. Framingham Heart Study, Framingham, Massachusetts, USA
    L Adrienne Cupples
  29. Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Kathryn E Davis & Deborah J Clegg
  30. Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) (CB06/03/0010), Girona, Spain
    José Manuel Fernández-Real & José Maria Moreno
  31. Intramural Research Program, National Institute on Aging, US National Institutes of Health, Bethesda, Maryland, USA
    Melissa Garcia, Lauren J Kim & Tamara B Harris
  32. Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
    Nicole L Glazer, Barbara McKnight & Bruce M Psaty
  33. Department of Medicine, University of Washington, Seattle, Washington, USA
    Nicole L Glazer
  34. Department of Medicine, Centre for Cardiovascular Genetics, University College London, London, UK
    Steve E Humphries & Philippa J Talmud
  35. Folkhälsan Research Centre, Helsinki, Finland
    Bo Isomaa
  36. Department of Social Services and Health Care, Jakobstad, Finland
    Bo Isomaa
  37. Population Studies Unit, National Institute for Health and Welfare, Helsinki, Finland
    Antti Jula
  38. Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, Massachusetts, USA
    David Karasik & Douglas P Kiel
  39. Department of Clinical Sciences, Lund University, Malmö, Sweden
    Magnus K Karlsson
  40. Department of Orthopaedics, Malmö University Hospital, Malmö, Sweden
    Magnus K Karlsson
  41. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
    Kay-Tee Khaw & Robert N Luben
  42. Department of Epidemiology and Public Health, University College London, London, UK
    Mika Kivimäki
  43. Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
    Yongmei Liu
  44. Department of Medical Sciences, Uppsala University, Uppsala, Sweden
    Östen Ljunggren
  45. Genetic, Research & Development, GlaxoSmithKline, King of Prussia, Philadelphia, USA
    Vincent Mooser & Kijoung S Song
  46. Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland
    Satu Männistö & Veikko Salomaa
  47. Institute of Cell & Molecular Biosciences, Newcastle University, Newcastle, UK
    Laura Pascoe & Mark Walker
  48. Instituto de Investigaciones Biomédicas, Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC) & Universidad Autónoma de Madrid, Madrid, Spain
    Belén Peral
  49. Department of Medicine, University of Washington, Seattle, Washington, USA
    Bruce M Psaty
  50. Department of Epidemiology, University of Washington, Seattle, Washington, USA
    Bruce M Psaty
  51. Department of Health Services, University of Washington, Seattle, Washington, USA
    Bruce M Psaty
  52. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA
    Bruce M Psaty
  53. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
    David B Savage, Robert K Semple, Antonio Vidal-Puig, Inês Barroso & Stephen O'Rahilly
  54. Institute for Anthropological Research, Zagreb, Croatia
    Tatjana Skaric-Juric
  55. Department of Endocrinology and Metabolism, University Hospital, Reykjavik, Iceland
    Gunnar Sigurdsson
  56. Faculty of Medicine, University of Iceland, Reykjavik, Iceland
    Gunnar Sigurdsson, Unnur Thorsteinsdottir & Kari Stefansson
  57. Department of Medical Sciences, Molecular Medicine, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
    Ann-Christine Syvänen
  58. National Genetics Institute (NGI), Centre for Medical Systems Biology (CMSB), Leiden, The Netherlands
    Cornelia M van Duijn
  59. Pacific Biosciences, Menlo Park, California, USA
    Eric Schadt
  60. Sage Bionetworks, Seattle, Washington, USA
    Eric Schadt
  61. Croatian Centre for Global Health, University of Split Medical School, Split, Croatia
    Igor Rudan
  62. Gen Info Ltd, Zagreb, Croatia
    Igor Rudan
  63. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland, USA
    Alan R Shuldiner
  64. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
    Erik Ingelsson
  65. Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    John-Olov Jansson
  66. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York, USA
    Robert C Kaplan
  67. University of Iceland, Reykjavik, Iceland
    Vilmundur Gudnason
  68. Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmö, Sweden
    Leif Groop
  69. Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
    Peter Vollenweider & Gérard Waeber
  70. National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK
    Jaspal S Kooner
  71. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Joel N Hirschhorn
  72. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität and Klinikum Großhadern, Munich, Germany
    H-Erich Wichmann
  73. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
    Elizabeth K Speliotes
  74. National Heart, Lung, and Blood Institute and Harvard Medical School, Boston, Massachusetts, USA
    Caroline S Fox

Authors

  1. Tuomas O Kilpeläinen
  2. M Carola Zillikens
  3. Alena Stančákova
  4. Francis M Finucane
  5. Janina S Ried
  6. Claudia Langenberg
  7. Weihua Zhang
  8. Jacques S Beckmann
  9. Jian'an Luan
  10. Liesbeth Vandenput
  11. Unnur Styrkarsdottir
  12. Yanhua Zhou
  13. Albert Vernon Smith
  14. Jing-Hua Zhao
  15. Najaf Amin
  16. Sailaja Vedantam
  17. So-Youn Shin
  18. Talin Haritunians
  19. Mao Fu
  20. Mary F Feitosa
  21. Meena Kumari
  22. Emmi Tikkanen
  23. Massimo Mangino
  24. Caroline Hayward
  25. Ci Song
  26. Alice M Arnold
  27. Yurii S Aulchenko
  28. Ben A Oostra
  29. Harry Campbell
  30. L Adrienne Cupples
  31. Kathryn E Davis
  32. Angela Döring
  33. Gudny Eiriksdottir
  34. Karol Estrada
  35. José Manuel Fernández-Real
  36. Melissa Garcia
  37. Christian Gieger
  38. Nicole L Glazer
  39. Candace Guiducci
  40. Albert Hofman
  41. Steve E Humphries
  42. Bo Isomaa
  43. Leonie C Jacobs
  44. Antti Jula
  45. David Karasik
  46. Magnus K Karlsson
  47. Kay-Tee Khaw
  48. Lauren J Kim
  49. Mika Kivimäki
  50. Norman Klopp
  51. Brigitte Kühnel
  52. Johanna Kuusisto
  53. Yongmei Liu
  54. Östen Ljunggren
  55. Mattias Lorentzon
  56. Robert N Luben
  57. Barbara McKnight
  58. Dan Mellström
  59. Braxton D Mitchell
  60. Vincent Mooser
  61. José Maria Moreno
  62. Satu Männistö
  63. Jeffery R O'Connell
  64. Laura Pascoe
  65. Leena Peltonen
  66. Belén Peral
  67. Markus Perola
  68. Bruce M Psaty
  69. Veikko Salomaa
  70. David B Savage
  71. Robert K Semple
  72. Tatjana Skaric-Juric
  73. Gunnar Sigurdsson
  74. Kijoung S Song
  75. Timothy D Spector
  76. Ann-Christine Syvänen
  77. Philippa J Talmud
  78. Gudmar Thorleifsson
  79. Unnur Thorsteinsdottir
  80. André G Uitterlinden
  81. Cornelia M van Duijn
  82. Antonio Vidal-Puig
  83. Sarah H Wild
  84. Alan F Wright
  85. Deborah J Clegg
  86. Eric Schadt
  87. James F Wilson
  88. Igor Rudan
  89. Samuli Ripatti
  90. Ingrid B Borecki
  91. Alan R Shuldiner
  92. Erik Ingelsson
  93. John-Olov Jansson
  94. Robert C Kaplan
  95. Vilmundur Gudnason
  96. Tamara B Harris
  97. Leif Groop
  98. Douglas P Kiel
  99. Fernando Rivadeneira
  100. Mark Walker
  101. Inês Barroso
  102. Peter Vollenweider
  103. Gérard Waeber
  104. John C Chambers
  105. Jaspal S Kooner
  106. Nicole Soranzo
  107. Joel N Hirschhorn
  108. Kari Stefansson
  109. H-Erich Wichmann
  110. Claes Ohlsson
  111. Stephen O'Rahilly
  112. Nicholas J Wareham
  113. Elizabeth K Speliotes
  114. Caroline S Fox
  115. Markku Laakso
  116. Ruth J F Loos

Contributions

A full list of author contributions appears in the Supplementary Note.

Corresponding author

Correspondence toRuth J F Loos.

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Competing interests

I.B. and spouse own stock in Incyte Ltd and GlaxoSmithKline. K.S., G.T., U.T. and U.S. are employed by deCODE Genetics. V.M. is a full-time employee of GlaxoSmithKline. G.W. and P.V. received funding from GlaxoSmithKline to build the CoLaus Study.

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Kilpeläinen, T., Zillikens, M., Stančákova, A. et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.Nat Genet 43, 753–760 (2011). https://doi.org/10.1038/ng.866

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