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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Nature Geneticsvolume 51pages452469 (2019) | Download Citation

Abstract

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

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Change history

  • 07 March 2019

    In the HTML version of the article originally published, the link for Supplementary Data 5 returned the file for Supplementary Data 7. The error has been corrected in the HTML version of the article.

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Acknowledgements

This work was primarily supported through funding from the National Institute of Health (NIH): 1K99HL130580, R01-DK089256, 2R01HD057194, U01HG007416, R01DK101855, T32 HL007055, KL2TR001109; and the American Heart Association (AHA): 13POST16500011 and 13GRNT16490017. Co-author Y. Jia recently passed away while this work was in process. This study was completed as part of the Genetic Investigation of ANtropometric Traits (GIANT) Consortium. This research has been conducted using the UK Biobank resource. A full list of acknowledgements is provided in the Supplementary Data 18.

Author information

Author notes

  1. These authors contributed equally: Anne E. Justice, Tugce Karaderi, Heather M. Highland, Kristin L. Young, Mariaelisa Graff, Yingchang Lu, Valérie Turcot.

  2. These authors jointly supervised this work: L. Adrienne Cupples, Ruth J.F. Loos, Kari E. North and Cecilia M. Lindgren.

  3. A list of members and affiliations appears in the Supplementary Note.

Affiliations

  1. Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA

    • Anne E. Justice
    • , Heather M. Highland
    • , Kristin L. Young
    •  & Mariaelisa Graff
  2. Weis Center for Research, Geisinger Health System, Danville, PA, USA

    • Anne E. Justice
  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    • Tugce Karaderi
    • , Anubha Mahajan
    • , Wei Gan
    • , Hidetoshi Kitajima
    • , Mark I. McCarthy
    • , Andrew P. Morris
    • , Neil R. Robertson
    • , Lorraine Southam
    •  & Cecilia M. Lindgren
  4. Department of Biological Sciences, Faculty of Arts and Sciences, Eastern Mediterranean University, Famagusta, Cyprus

    • Tugce Karaderi
  5. Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA

    • Heather M. Highland
    • , Eric Boerwinkle
    •  & Megan L. Grove
  6. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    • Yingchang Lu
  7. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Yingchang Lu
    • , Claudia Schurmann
    • , Tamuno Alfred
    • , Erwin P. Bottinger
    •  & Ruth J. F. Loos
  8. The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Yingchang Lu
    • , Claudia Schurmann
    •  & Ruth J. F. Loos
  9. Montreal Heart Institute, Universite de Montreal, Montreal, Quebec, Canada

    • Valérie Turcot
    • , Ken Sin Lo
    • , Simon de Denus
    • , Marie-Pierre Dubé
    • , Jean-Claude Tardif
    •  & Guillaume Lettre
  10. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA

    • Paul L. Auer
  11. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    • Rebecca S. Fine
    • , Tõnu Esko
    • , Sailaja Vedantam
    • , Alisa K. Manning
    • , Daniel I. Chasman
    • , Jose C. Florez
    •  & Joel N. Hirschhorn
  12. Department of Genetics, Harvard Medical School, Boston, MA, USA

    • Rebecca S. Fine
    •  & Sailaja Vedantam
  13. Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA, USA

    • Rebecca S. Fine
    • , Tõnu Esko
    • , Sailaja Vedantam
    •  & Joel N. Hirschhorn
  14. Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA

    • Xiuqing Guo
    • , Zorayr Arzumanyan
    • , Yii-Der Ida Chen
    • , Yucheng Jia
    • , Kent D. Taylor
    • , Jie Yao
    •  & Jerome I. Rotter
  15. Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

    • Adelheid Lempradl
    •  & J. Andrew Pospisilik
  16. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    • Eirini Marouli
    • , Mark J. Caulfield
    • , Patricia B. Munroe
    • , Ioanna Ntalla
    • , Kathleen E. Stirrups
    • , Helen R. Warren
    •  & Panos Deloukas
  17. Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany

    • Thomas W. Winkler
    • , Mathias Gorski
    •  & Iris M. Heid
  18. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA

    • Adam E. Locke
    • , Goncalo Abecasis
    • , Michael Boehnke
    • , Shuang Feng
    • , Anne U. Jackson
    • , Xueling Sim
    •  & Heather M. Stringham
  19. McDonnell Genome Institute, Washington University School of Medicine, Saint Louis, MO, USA

    • Adam E. Locke
  20. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    • Carolina Medina-Gomez
    • , M. Arfan Ikram
    • , André G. Uitterlinden
    • , Cornelia M. van Duijn
    • , M. Carola Zillikens
    •  & Fernando Rivadeneira
  21. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    • Carolina Medina-Gomez
    • , Linda Broer
    • , André G. Uitterlinden
    • , M. Carola Zillikens
    •  & Fernando Rivadeneira
  22. Estonian Genome Center, University of Tartu, Tartu, Estonia

    • Tõnu Esko
    • , Reedik Mägi
    •  & Evelin Mihailov
  23. Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA

    • Ayush Giri
    •  & Ken Sin Lo
  24. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Poorva Mudgal
    • , Maggie C. Y. Ng
    • , Donald W. Bowden
    •  & Amanda J. Cox
  25. Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Maggie C. Y. Ng
    • , Donald W. Bowden
    •  & Amanda J. Cox
  26. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    • Nancy L. Heard-Costa
  27. NHLBI Framingham Heart Study, Framingham, MA, USA

    • Nancy L. Heard-Costa
    • , Caroline S. Fox
    •  & L. Adrienne Cupples
  28. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

    • Mary F. Feitosa
    •  & Ingrid B. Borecki
  29. Department of Medicine, Harvard University Medical School, Boston, MA, USA

    • Alisa K. Manning
    •  & Jose C. Florez
  30. Massachusetts General Hospital, Boston, MA, USA

    • Alisa K. Manning
    • , Suthesh Sivapalaratnam
    •  & Jose C. Florez
  31. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK

    • Sara M. Willems
    • , Claudia Langenberg
    • , Jian’an Luan
    • , John R. B. Perry
    • , Robert A. Scott
    • , Nicholas J. Wareham
    •  & Jing Hua Zhao
  32. Department of Vascular Medicine, AMC, Amsterdam, The Netherlands

    • Suthesh Sivapalaratnam
  33. Department of Haematology, University of Cambridge, Cambridge, UK

    • Suthesh Sivapalaratnam
    •  & Kathleen E. Stirrups
  34. School of Public Health, University of Michigan, Ann Arbor, MI, USA

    • Goncalo Abecasis
  35. School of Kinesiology and Health Science, Faculty of Health, York University, Toronto, Canada

    • Dewan S. Alam
  36. Department of Family Medicine & Public Health, University of California, San Diego, La Jolla, CA, USA

    • Matthew Allison
  37. INSERM U1167, Lille, France

    • Philippe Amouyel
  38. Institut Pasteur de Lille, U1167, Lille, France

    • Philippe Amouyel
  39. U1167—RID-AGE, Universite de Lille - Risk factors and molecular determinants of aging-related diseases, Lille, France

    • Philippe Amouyel
  40. INSERM U1018, Centre de recherche en Épidemiologie et Sante des Populations (CESP), Villejuif, France

    • Beverley Balkau
  41. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA

    • Lisa Bastarache
    •  & Josh C. Denny
  42. Department of Computational Biology, University of Lausanne, Lausanne, Switzerland

    • Sven Bergmann
    •  & David Lamparter
  43. Swiss Institute of Bioinformatics, Lausanne, Switzerland

    • Sven Bergmann
    • , David Lamparter
    •  & Zoltán Kutalik
  44. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    • Lawrence F. Bielak
    • , Sharon L. R. Kardia
    •  & Jennifer A. Smith
  45. IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany

    • Matthias Blüher
    • , Peter Kovacs
    •  & Michael Stumvoll
  46. Department of Medicine, University of Leipzig, Leipzig, Germany

    • Matthias Blüher
    •  & Michael Stumvoll
  47. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany

    • Heiner Boeing
  48. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

    • Eric Boerwinkle
  49. Department of Nephrology, University Hospital Regensburg, Regensburg, Germany

    • Carsten A. Böger
    •  & Mathias Gorski
  50. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Jette Bork-Jensen
    • , Niels Grarup
    • , Torben Hansen
    • , Johanne M. Justesen
    • , Oluf Pedersen
    • , Tune H. Pers
    •  & Henrik Vestergaard
  51. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Donald W. Bowden
  52. Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark

    • Ivan Brandslund
  53. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

    • Ivan Brandslund
  54. Department of Medicine (Medical Genetics), University of Washington, Seattle, WA, USA

    • Amber A. Burt
    • , Gail P. Jarvik
    •  & Eric B. Larson
  55. MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Adam S. Butterworth
    • , Rajiv Chowdhury
    • , John Danesh
    • , Emanuele Di Angelantonio
    • , Joanna M. M. Howson
    • , Praveen Surendran
    •  & Robin Young
  56. NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Adam S. Butterworth
    • , John Danesh
    •  & Emanuele Di Angelantonio
  57. NIHR Barts Cardiovascular Research Centre, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK

    • Mark J. Caulfield
    • , Patricia B. Munroe
    •  & Helen R. Warren
  58. Research Centre on Public Health, University of Milano-Bicocca, Monza, Italy

    • Giancarlo Cesana
  59. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

    • John C. Chambers
  60. Department of Cardiology, London North West Healthcare NHS Trust, Ealing Hospital, Middlesex, UK

    • John C. Chambers
    • , Jaspal S. Kooner
    •  & Weihua Zhang
  61. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    • John C. Chambers
    • , Evangelos Evangelou
    • , Marcelo Segura-Lepe
    •  & Weihua Zhang
  62. Imperial College Healthcare NHS Trust, London, UK

    • John C. Chambers
    •  & Jaspal S. Kooner
  63. MRC-PHE Centre for Environment and Health, Imperial College London, London, UK

    • John C. Chambers
    •  & Jaspal S. Kooner
  64. Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    • Daniel I. Chasman
  65. Division of Preventive Medicine, Brigham and Women’s and Harvard Medical School, Boston, MA, USA

    • Daniel I. Chasman
    • , Audrey Y. Chu
    •  & Paul M. Ridker
  66. Harvard Medical School, Boston, MA, USA

    • Daniel I. Chasman
    •  & Paul M. Ridker
  67. Medical department, Lillebaelt Hospital, Vejle, Denmark

    • Cramer Christensen
  68. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

    • Francis S. Collins
    •  & Narisu Narisu
  69. Department of Biostatistics, University of Liverpool, Liverpool, UK

    • James P. Cook
    •  & Andrew P. Morris
  70. Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia

    • Amanda J. Cox
  71. Department of Biomedical Infomatics and Medical Education, University of Washington, Seattle, WA, USA

    • David S. Crosslin
  72. Wellcome Trust Sanger Institute, Hinxton, UK

    • John Danesh
    • , Gaëlle Marenne
    • , Lorraine Southam
    •  & Eleftheria Zeggini
  73. British Heart Foundation Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, UK

    • John Danesh
    •  & Emanuele Di Angelantonio
  74. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    • Paul I. W. de Bakker
  75. Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands

    • Paul I. W. de Bakker
  76. Faculty of Pharmacy, Universite de Montreal, Montreal, Quebec, Canada

    • Simon de Denus
  77. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

    • Renée de Mutsert
    • , Ruifang Li-Gao
    •  & Dennis O. Mook-Kanamori
  78. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece

    • George Dedoussis
    •  & Aliki-Eleni Farmaki
  79. Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA

    • Ellen W. Demerath
  80. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    • Joe G. Dennis
    • , Douglas F. Easton
    • , Ailith Ewing
    •  & Deborah J. Thompson
  81. Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany

    • Marcus Dörr
  82. DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, Germany

    • Marcus Dörr
  83. Institute of Cardiovascular Science, University College London, London, UK

    • Fotios Drenos
  84. MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK

    • Fotios Drenos
  85. Department of Life Sciences, Brunel University London, Uxbridge, UK

    • Fotios Drenos
  86. Department of Medicine, Faculty of Medicine, Universite de Montreal, Montreal, Quebec, Canada

    • Marie-Pierre Dubé
    • , Jean-Claude Tardif
    •  & Guillaume Lettre
  87. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK

    • Alison M. Dunning
    •  & Douglas F. Easton
  88. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK

    • Paul Elliott
  89. Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece

    • Evangelos Evangelou
  90. CNR Institute of Clinical Physiology, Pisa, Italy

    • Ele Ferrannini
  91. Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy

    • Ele Ferrannini
  92. Toulouse University School of Medicine, Toulouse, France

    • Jean Ferrieres
  93. Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA

    • Myriam Fornage
    •  & Li-An Lin
  94. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden

    • Paul W. Franks
  95. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    • Paul W. Franks
  96. Department of Public Health and Clinical Medicine, Unit of Medicine, Umeå University, Umeå, Sweden

    • Paul W. Franks
  97. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

    • Nele Friedrich
  98. Ilaria Gandin, Research Unit, AREA Science Park, Trieste, Italy

    • Ilaria Gandin
  99. Department of Medical Sciences, University of Trieste, Trieste, Italy

    • Paolo Gasparini
    • , Giorgia Girotto
    • , Anna Morgan
    •  & Dragana Vuckovic
  100. Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy

    • Paolo Gasparini
    • , Giorgia Girotto
    •  & Dragana Vuckovic
  101. Geriatrics, Department of Public Health, Uppsala University, Uppsala, Sweden

    • Vilmantas Giedraitis
  102. German Center for Diabetes Research, München-Neuherberg, Germany

    • Harald Grallert
    • , Karina Meidtner
    •  & Matthias B. Schulze
  103. Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

    • Harald Grallert
  104. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

    • Harald Grallert
  105. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    • Stefan Gustafsson
    •  & Erik Ingelsson
  106. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle WA, USA

    • Jeff Haessler
    •  & Alex P. Reiner
  107. University of Exeter Medical School, University of Exeter, Exeter, UK

    • Andrew T. Hattersley
  108. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    • Caroline Hayward
    • , Jonathan Marten
    •  & Veronique Vitart
  109. Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

    • Iris M. Heid
    • , Martina Müller-Nurasyid
    •  & Konstantin Strauch
  110. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, NTNU, Norwegian University of Science and Technology, Trondheim, Norway

    • Oddgeir L. Holmen
    •  & Kristian Hveem
  111. Department of Vascular Medicine, AMC, Amsterdam, The Netherlands

    • G. Kees Hovingh
  112. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    • Yao Hu
    • , Huaixing Li
    • , Xu Lin
    • , Liang Sun
    • , Feijie Wang
    •  & He Zheng
  113. Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan

    • Yi-Jen Hung
  114. School of Medicine, National Defense Medical Center, Taipei, Taiwan

    • Yi-Jen Hung
  115. HUNT Research Center, Department of Public Health, Norwegian University of Science and Technology, Levanger, Norway

    • Kristian Hveem
  116. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands

    • M. Arfan Ikram
  117. Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands

    • M. Arfan Ikram
  118. Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA

    • Erik Ingelsson
  119. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    • Gail P. Jarvik
  120. Faculty of Medicine, Aalborg University, Aalborg, Denmark

    • Torben Jørgensen
  121. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Torben Jørgensen
  122. Research Center for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark

    • Torben Jørgensen
    • , Allan Linneberg
    •  & Betina H. Thuesen
  123. National Institute for Health and Welfare, Helsinki, Finland

    • Pekka Jousilahti
    • , Kari Kuulasmaa
    • , Jaana Lindström
    • , Satu Männistö
    • , Markus Perola
    • , Veikko Salomaa
    •  & Jaakko Tuomilehto
  124. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA

    • Bratati Kahali
    • , Elizabeth K. Speliotes
    • , Cristen J. Willer
    •  & Wei Zhou
  125. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    • Bratati Kahali
    • , Elizabeth K. Speliotes
    • , Cristen J. Willer
    •  & Wei Zhou
  126. Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA

    • Bratati Kahali
    •  & Elizabeth K. Speliotes
  127. Centre for Brain Research, Indian Institute of Science, Bangalore, India

    • Bratati Kahali
  128. Echinos Medical Centre, Echinos, Greece

    • Maria Karaleftheri
  129. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    • Fredrik Karpe
    • , Mark I. McCarthy
    • , Matt Neville
    • , Katharine R. Owen
    •  & Neil R. Robertson
  130. Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK

    • Fredrik Karpe
    • , Mark I. McCarthy
    • , Matt Neville
    •  & Katharine R. Owen
  131. UKCRC Centre of Excellence for Public Health Research, Queens University Belfast, Belfast, UK

    • Frank Kee
  132. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland

    • Pirjo Komulainen
    • , Timo A. Lakka
    •  & Rainer Rauramaa
  133. National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, London, UK

    • Jaspal S. Kooner
  134. University Medical Centre Mannheim, 5th Medical Department, University of Heidelberg, Mannheim, Germany

    • Bernhard K. Krämer
  135. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

    • Johanna Kuusisto
    •  & Markku Laakso
  136. Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Finland

    • Timo A. Lakka
    •  & Rainer Rauramaa
  137. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland

    • Timo A. Lakka
  138. Verge Genomics, San Fransico, CA, USA

    • David Lamparter
  139. Division of Biomedical and Personalized Medicine, Department of Medicine, University of Colorado-Denver, Aurora, CO, USA

    • Leslie A. Lange
  140. Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA

    • Eric B. Larson
  141. Department of Health Services, University of Washington, Seattle, WA, USA

    • Eric B. Larson
  142. Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, Philippines

    • Nanette R. Lee
  143. USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines

    • Nanette R. Lee
  144. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

    • Wen-Jane Lee
  145. Department of Social Work, Tunghai University, Taichung, Taiwan

    • Wen-Jane Lee
  146. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland

    • Terho Lehtimäki
    •  & Leo-Pekka Lyytikäinen
  147. Department of Clinical Chemistry, Finnish Cardiovascular Research Center—Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    • Terho Lehtimäki
    •  & Leo-Pekka Lyytikäinen
  148. Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    • Cora E. Lewis
  149. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA

    • Jin Li
  150. Uppsala University, Uppsala, Sweden

    • Lars Lind
  151. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark

    • Allan Linneberg
  152. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    • Allan Linneberg
  153. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    • Ching-Ti Liu
    • , Gina M. Peloso
    • , Shuai Wang
    •  & L. Adrienne Cupples
  154. Department of Public Health Sciences, Institute for Personalized Medicine, The Pennsylvania State University College of Medicine, Hershey, PA, USA

    • Dajiang J. Liu
  155. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    • Stuart MacGregor
  156. Department of Cardiovascular Sciences, Univeristy of Leicester, Glenfield Hospital, Leicester, UK

    • Nicholas G. D. Masca
    • , Christopher P. Nelson
    •  & Nilesh J. Samani
  157. NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK

    • Nicholas G. D. Masca
    • , Christopher P. Nelson
    •  & Nilesh J. Samani
  158. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany

    • Karina Meidtner
    •  & Matthias B. Schulze
  159. Department of Medicine, Kuopio University Hospital, Kuopio, Finland

    • Leena Moilanen
  160. Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, France

    • Marie Moitry
  161. Department of Public Health, University Hospital of Strasbourg, Strasbourg, France

    • Marie Moitry
  162. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands

    • Dennis O. Mook-Kanamori
  163. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universitat, Munich, Germany

    • Martina Müller-Nurasyid
  164. DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany

    • Martina Müller-Nurasyid
  165. Program for Personalized and Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    • Jeffrey R. O’Connell
    • , James A. Perry
    •  & Laura M. Yerges-Armstrong
  166. Division of Obstetric and Gynaecology, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia

    • Craig E. Pennell
    •  & Carol A. Wang
  167. School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, New South Wales, Australia

    • Craig E. Pennell
    •  & Carol A. Wang
  168. Institute for Molecular Medicine (FIMM) and Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland

    • Markus Perola
  169. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

    • Tune H. Pers
  170. School of Medicine, University of Split, Split, Croatia

    • Ozren Polasek
  171. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK

    • Ozren Polasek
    •  & Igor Rudan
  172. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland

    • Olli T. Raitakari
  173. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

    • Olli T. Raitakari
  174. Centre for Non-Communicable Diseases, Karachi, Pakistan

    • Asif Rasheed
    •  & Danish Saleheen
  175. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    • Chelsea K. Raulerson
    • , Ying Wu
    •  & Karen L. Mohlke
  176. Genetics and Pharmacogenomics, Merck & Co., Inc., Boston, MA, USA

    • Dermot F. Reilly
  177. Department of Epidemiology, University of Washington, Seattle, WA, USA

    • Alex P. Reiner
  178. Division of Cardiovascular Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    • Paul M. Ridker
  179. Department of Biomedical Data Science, Stanford University, Stanford, CA, USA

    • Manuel A. Rivas
  180. Institute for Maternal and Child Health, IRCCS ‘Burlo Garofolo’, Trieste, Italy

    • Antonietta Robino
  181. Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK

    • Katherine S. Ruth
    • , Andrew R. Wood
    • , Hanieh Yaghootkar
    •  & Timothy M. Frayling
  182. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    • Danish Saleheen
    •  & Wei Zhao
  183. Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN, USA

    • Pamela J. Schreiner
  184. Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore

    • Xueling Sim
  185. Genetics, Target Sciences, GlaxoSmithKline, Research Triangle Park, NC, USA

    • Andrew J. Slater
  186. OmicSoft a QIAGEN Company, Cary, NC, USA

    • Andrew J. Slater
  187. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK

    • Kerrin S. Small
    •  & Timothy D. Spector
  188. Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

    • Blair H. Smith
  189. Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK

    • Blair H. Smith
  190. deCODE Genetics/Amgen Inc., Reykjavik, Iceland

    • Kari Stefansson
    • , Valgerdur Steinthorsdottir
    • , Gudmar Thorleifsson
    •  & Unnur Thorsteinsdottir
  191. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    • Kari Stefansson
    •  & Unnur Thorsteinsdottir
  192. Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany

    • Konstantin Strauch
  193. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

    • Karin M. A. Swart
  194. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    • Alexander Teumer
  195. Center for Pediatric Research, Department for Women’s and Child Health, University of Leipzig, Leipzig, Germany

    • Anke Tönjes
  196. USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

    • Mina Torres
    •  & Rohit Varma
  197. Anogia Medical Centre, Anogia, Greece

    • Emmanouil Tsafantakis
  198. Centre for Vascular Prevention, Danube-University Krems, Krems, Austria

    • Jaakko Tuomilehto
  199. Dasman Diabetes Institute, Dasman, Kuwait

    • Jaakko Tuomilehto
  200. Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia

    • Jaakko Tuomilehto
  201. Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    • Matti Uusitupa
  202. Central Finland Central Hospital, Jyvaskyla, Finland

    • Mauno Vanhala
  203. University of Eastern Finland, Kuopio, Finland

    • Mauno Vanhala
  204. Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    • Sita H. Vermeulen
  205. Steno Diabetes Center Copenhagen, Gentofte, Denmark

    • Henrik Vestergaard
  206. Cardiometabolic Disease, Merck & Co., Inc., Kenilworth, NJ, USA

    • Thomas F. Vogt
  207. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA

    • Lynne E. Wagenknecht
  208. Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle, UK

    • Mark Walker
  209. Department of Medical Sciences, Cardiology, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

    • Lars Wallentin
  210. Genetics, Target Sciences, GlaxoSmithKline, Collegeville, PA, USA

    • Dawn M. Waterworth
  211. Departments of Epidemiology & Medicine, Diabetes Translational Research Center, Fairbanks School of Public Health & School of Medicine, Indiana University, Indiana, IN, USA

    • Jennifer Wessel
  212. Green Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland, New Zealand

    • Harvey D. White
  213. Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA

    • Cristen J. Willer
  214. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

    • James G. Wilson
  215. GlaxoSmithKline, King of Prussia, PA, USA

    • Laura M. Yerges-Armstrong
  216. University of Glasgow, Glasgow, UK

    • Robin Young
  217. Department of Clinical Sciences, Quantitative Biomedical Research Center, Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX, USA

    • Xiaowei Zhan
  218. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia

    • Panos Deloukas
  219. Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland

    • Zoltán Kutalik
  220. Departments of Pediatrics and Genetics, Harvard Medical School, Boston, MA, USA

    • Joel N. Hirschhorn
  221. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    • Ruth J. F. Loos
  222. Department of Epidemiology and Carolina Center of Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    • Kari E. North
  223. Li Ka Shing Centre for Health Information and Discovery, The Big Data Institute, University of Oxford, Oxford, UK

    • Cecilia M. Lindgren

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