Biological, clinical and population relevance of 95 loci for blood lipids (original) (raw)

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Acknowledgements

We wish to dedicate this paper to the memory of Dr Leena Peltonen, who passed away on 11 March 2010. A full listing of acknowledgements is provided in Supplementary Information.

Author information

Author notes

1. Tanya M. Teslovich, Kiran Musunuru, L. Adrienne Cupples, Manjinder S. Sandhu, Paul M Ridker, Daniel J. Rader, Cornelia M. van Duijn, Gonçalo R. Abecasis, Michael Boehnke and Sekar Kathiresan: These authors contributed equally to this work.
2. Leena Peltonen: Deceased.

Authors and Affiliations

1. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, Michigan, USA
   Tanya M. Teslovich, Cristen J. Willer, Heather M. Stringham, Gonçalo R. Abecasis & Michael Boehnke
2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
   Kiran Musunuru, James P. Pirruccello, Benjamin F. Voight, David Altshuler & Sekar Kathiresan
3. Cardiovascular Research Center, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA
   Kiran Musunuru & Sekar Kathiresan
4. Department of Medicine, Harvard Medical School, Boston, 02115, Massachusetts, USA
   Kiran Musunuru, Daniel I. Chasman, Robert Y. L. Zee, Christopher J. O’Donnell, David Altshuler, Paul M Ridker & Sekar Kathiresan
5. Broad Institute, Cambridge, 02142, Massachusetts, USA
   Kiran Musunuru, James P. Pirruccello, Benjamin F. Voight, Candace Guiducci, Elena Gonzalez, Kenechi G. Ejebe, Gabriel Crawford, Noel P. Burtt, David Altshuler, Stacey B. Gabriel & Sekar Kathiresan
6. Johns Hopkins University School of Medicine, Baltimore, 21287, Maryland, USA
   Kiran Musunuru & James P. Pirruccello
7. Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Kopavogur, 201, Iceland
   Albert V. Smith & Vilmundur Gudnason
8. University of Iceland, Reykjavik, 101, Iceland
   Albert V. Smith, Unnur Thorsteinsdottir, Vilmundur Gudnason & Kari Stefansson
9. Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
   Andrew C. Edmondson, Mingyao Li, Muredach P. Reilly & Daniel J. Rader
10. Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Andrew C. Edmondson, Ioannis M. Stylianou, Mingyao Li, Muredach P. Reilly & Daniel J. Rader
11. Division of Molecular Medicine, Department of Medicine, Columbia University, New York, 10032, New York, USA
    Masahiro Koseki, David Masson & Alan R. Tall
12. Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, FI-00014, Finland
    Samuli Ripatti, Ida Surakka, Kaisa Silander, Juha Saharinen, Markus Perola & Jaakko Kaprio
13. National Institute for Health and Welfare, P.O. Box 104, FI-00251 Helsinki, Finland.,
    Samuli Ripatti, Ida Surakka, Kaisa Silander, Markus Perola & Jaakko Kaprio
14. Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, 02215, Massachusetts, USA
    Daniel I. Chasman, Robert Y. L. Zee, Lynda M. Rose & Paul M Ridker
15. Robarts Research Institute, University of Western Ontario, London, N6A 5K8, Ontario, Canada
    Christopher T. Johansen & Robert A. Hegele
16. Department of Vascular Medicine, Academic Medical Centre at the University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands
    Sigrid W. Fouchier, G. Kees Hovingh & John J.P. Kastelein
17. Department of Epidemiology, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.,
    Aaron Isaacs, Yurii S. Aulchenko, Jacqueline C. M. Witteman, Andre G. Uitterlinden, Eric J. G. Sijbrands, A. Cecile J. W. Janssens, Albert Hofman & Cornelia M. van Duijn
18. Department of Biostatistics, Boston University School of Public Health, Boston, 02118, Massachusetts, USA
    Gina M. Peloso, Serkalem Demissie & L. Adrienne Cupples
19. National Heart, Lung and Blood Institute’s Framingham Heart Study, Framingham, 01702, Massachusetts, USA
    Gina M. Peloso, Christopher J. O’Donnell, Serkalem Demissie & L. Adrienne Cupples
20. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, 77030, Texas, USA
    Maja Barbalic & Eric Boerwinkle
21. Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, CB1 8RN, UK
    Sally L. Ricketts, Robert Luben, Kay-Tee Khaw & Manjinder S. Sandhu
22. Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, 98101, Washington, USA
    Joshua C. Bis
23. deCODE Genetics, Reykjavik, 101, Iceland
    Gudmar Thorleifsson, Hilma Holm, Unnur Thorsteinsdottir & Kari Stefansson
24. Division of Statistical Genomics in the Center for Genome Sciences, Washington University School of Medicine, St Louis, 63108, Missouri, USA
    Mary F. Feitosa & Ingrid B. Borecki
25. Department of Epidemiology and Public Health, Imperial College London, London, W2 1PG, UK
    John Chambers & Weihua Zhang
26. Department of Clinical Sciences, Lund University, Malmö, SE-20502, Sweden
    Marju Orho-Melander, Olle Melander & Leif C. Groop
27. Clinical Pharmacology and Barts and the London Genome Centre, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, UK
    Toby Johnson & Mark J. Caulfield
28. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, 90048, California, USA
    Xiaohui Li, Xiuqing Guo, Talin Haritunians, Yii-der I. Chen & Jerome I. Rotter
29. Center for Genome Science, National Institute of Health, Seoul, 122-701, Republic of Korea
    Yoon Shin Cho, Min Jin Go, Young Jin Kim & Jong-Young Lee
30. Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, 151-742, Republic of Korea
    Taesung Park
31. Department of Statistics, College of Natural Sciences, Seoul National University, Seoul, 151-742, Republic of Korea
    Taesung Park
32. Department of Statistics, Sookmyung Women’s University, Seoul, 140-742, Republic of Korea
    Kyunga Kim
33. Centre for Molecular Epidemiology, National University of Singapore, Singapore, 117597, Republic of Singapore
    Xueling Sim
34. Genome Institute of Singapore, Singapore, 138672, Republic of Singapore
    Rick Twee-Hee Ong & Mark Seielstad
35. Department of Genetics, University of North Carolina, Chapel Hill, 27599, North Carolina, USA
    Damien C. Croteau-Chonka, Leslie A. Lange & Karen L. Mohlke
36. Department of Genome Sciences, University of Washington, Seattle, 98195, Washington, USA
    Joshua D. Smith, Mark Rieder & Deborah A. Nickerson
37. Genetics Division, GlaxoSmithKline R&D, King of Prussia, 19406, Pennsylvania, USA
    Kijoung Song, Xin Yuan, Dawn M. Waterworth & Vincent Mooser
38. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK
    Jing Hua Zhao, Jian’an Luan, Nicholas J. Wareham, Ruth J. F. Loos, Claudia Langenberg & Manjinder S. Sandhu
39. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schoepfstrasse 41, A-6020 Innsbruck, Austria.,
    Claudia Lamina & Florian Kronenberg
40. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, 23562, Germany
    Andreas Ziegler & Inke R. König
41. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, EH4 2XU, UK
    Alan F. Wright, Veronique Vitart, Caroline Hayward & Nicholas D. Hastie
42. Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA) and Center of Medical Systems Biology (CMSB), Leiden, 2300 RC, The Netherlands
    Jacqueline C. M. Witteman, Andre G. Uitterlinden, Albert Hofman & Cornelia M. van Duijn
43. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, EH8 9AG, UK
    James F. Wilson, Igor Rudan & Harry Campbell
44. Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.,
    Gonneke Willemsen, Jouke-Jan Hottenga, Eco J. C. de Geus & Dorret I. Boomsma
45. Institute of Epidemiology, Helmholtz Zentrum Munchen – German Research Center for Environmental Health, Neuherberg, 85764, Germany
    H.-Erich Wichmann, Iris M. Heid, Christian Gieger & Angela Döring
46. Genetic Epidemiology Unit, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, 4029, Queensland, Australia
    John B. Whitfield, Grant W. Montgomery & Nicholas G. Martin
47. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland
    Gérard Waeber & Peter Vollenweider
48. Department of Internal Medicine, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.,
    Andre G. Uitterlinden & Eric J. G. Sijbrands
49. Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.,
    Manuela Uda & Serena Sanna
50. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, FI-00271, Finland
    Jaakko Tuomilehto, Veikko Salomaa & Aki S. Havulinna
51. Department of Health Sciences, University of Leicester, Leicester, LE1 6TP, UK
    John R. Thompson
52. Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, 21225, Maryland, USA
    Toshiko Tanaka
53. Medstar Research Institute, Baltimore, 21218, Maryland, USA
    Toshiko Tanaka
54. Department of Twin Research and Genetic Epidemiology, King’s College London, London, SE1 7EH, UK
    Tim D. Spector, Nicole Soranzo & Massimo Mangino
55. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.,
    Nicole Soranzo, Panagiotis Deloukas, Inês Barroso & Manjinder S. Sandhu
56. Department of Psychiatry, EMGO Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands
    Johannes H. Smit & Brenda W. J. H. Penninx
57. Division of Cardiology, Department of Medicine, Helsinki University Central Hospital (HUCH), Helsinki, FI-00029, Finland
    Juha Sinisalo & Markku S. Nieminen
58. Unita Operativa Geriatria, Istituto Nazionale Ricovero e Cura Anziani (INRCA), Istituto Ricovero e Cura a Carattere Scientifico (IRCCS), Via Cassia 1167, 00189 Rome, Italy.,
    Angelo Scuteri
59. Hammersmith Hospital, National Heart and Lung Institute, Imperial College London, London, W12 0NN, UK
    James Scott & Jaspal S. Kooner
60. Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA.,
    David Schlessinger & Edward G. Lakatta
61. Department of Health Research and Policy, Stanford University, Stanford, 94305, California, USA
    Chiara Sabatti
62. Department of Clinical Chemistry, University of Oulu, FI-90220, Oulu, Finland
    Aimo Ruokonen
63. The John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa, Ottawa, K1Y 4W7, Canada
    Robert Roberts & Ruth McPherson
64. Departments of Medicine, Epidemiology, and Health Services, University of Washington, Group Health Research Institute, Group Health Cooperative, Seattle, 98101, Washington, USA
    Bruce M. Psaty
65. Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso 1, 39100 Bolzano, Italy – affiliated institute of the University of Lübeck, Germany
    Peter P. Pramstaller, Irene Pichler, Cristian Pattaro & Andrew A. Hicks
66. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE-17177, Sweden
    Nancy L. Pedersen, Patrik K. E. Magnusson & Erik Ingelsson
67. Amgen, Thousand Oaks, California 91320, USA.,
    Alex N. Parker
68. Genetic and Molecular Epidemiology Laboratory, McMaster University, Hamilton, L8N3Z5, Ontario, Canada
    Guillaume Pare
69. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands
    Ben A. Oostra
70. Institut fur Humangenetik, Helmholtz Zentrum Munchen, Deutsches Forschungszentrum fur Umwelt und Gesundheit, Neuherberg, 85764, Germany
    Thomas Meitinger
71. Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, Muenchen, 81675, Germany
    Thomas Meitinger
72. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.,
    Mark I. McCarthy
73. Oxford Centre for Diabetes, Endocrinology and Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK
    Mark I. McCarthy
74. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LJ, UK
    Mark I. McCarthy
75. Avon Longitudinal Study of Parents and Children, University of Bristol, Bristol, BS8 2BN, UK
    Wendy McArdle
76. Institute of Applied Genomics, via Linussio 51, 33100 Udine, Italy.,
    Fabio Marroni
77. Cardiovascular Epidemiology and Genetics, Institut Municipal d’Investigacio Medica, Barcelona, 08003, Spain
    Gavin Lucas
78. Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, FI-00014, Finland
    Marja-Liisa Lokki
79. Montreal Heart Institute (Research Center), Université de Montréal, Montréal, H1T 1C8, Québec, Canada
    Guillaume Lettre
80. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, 20892, Maryland, USA
    Lenore J. Launer & Tamara B. Harris
81. Science Center, Tampere University Hospital, Tampere, FI-33521, Finland
    Reijo Laaksonen
82. Institute of Regional Health Research and the Danish Twin Registry, Institute of Public Health, University of Southern Denmark, JBWinsløws Vej 9B, DK-5000, Odense, Denmark.,
    Kirsten O. Kyvik
83. Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, FI-00014, Finland
    Jaakko Kaprio
84. Massachusetts General Hospital Weight Center, Boston, 02114, Massachusetts, USA
    Lee M. Kaplan
85. Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Uppsala, SE-75185, Sweden
    Åsa Johansson, Wilmar Igl & Ulf Gyllensten
86. Department of Epidemiology & Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London W2 1PG, UK.,
    Marjo-Riitta Jarvelin & Paul Elliott
87. Department of Public Health Science and General Practice, University of Oulu, Oulu, FI-90220, Finland
    Marjo-Riitta Jarvelin
88. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, 93053, Germany
    Christian Hengstenberg
89. Department of Epidemiology and Preventive Medicine Regensburg University Medical Center Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Germany
    Iris M. Heid
90. Department of Biomedical Engineering and Computational Science, Aalto University School of Science and Technology, Aalto, FI-00076, Finland
    Aki S. Havulinna
91. LIGHT Research Institute, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK
    Alistair S. Hall
92. Department of Medicine, Helsinki University Hospital, Helsinki, FI-00029, Finland
    Leif C. Groop
93. Department of Psychiatry, Center for Neurobehavioral Genetics, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, 90095, California, USA
    Nelson B. Freimer
94. Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, 21225, Maryland, USA
    Luigi Ferrucci
95. Medizinische Klinik II, Universität zu Lübeck, Lübeck, 23538, Germany
    Jeanette Erdmann & Heribert Schunkert
96. MRC-HPA Centre for Environment and Health, Imperial College London, London, W2 1PG, UK
    Paul Elliott
97. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.,
    Anna F. Dominiczak
98. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SE-17177, Sweden
    Ulf de Faire
99. National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA
    Francis S. Collins & Lori L. Bonnycastle
100. Departments of Vascular Medicine & Cardiology, Academic Medical Centre, Amsterdam, 1105 AZ, The Netherlands
     S. Matthijs Boekholdt
101. Department of Physiology and Biophysics, University of Southern California, Los Angeles, 90033, California, USA
     Richard N. Bergman
102. Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, 50125, Italy
     Stefania Bandinelli
103. Department of Medicine, Baylor College of Medicine, Houston, 77030, Texas, USA
     Christie M. Ballantyne
104. Department of Medicine, Stanford University School of Medicine, Stanford, 94305, California, USA
     Themistocles L. Assimes & Thomas Quertermous
105. Singapore Eye Research Institute, National University of Singapore, Singapore, 168751, Republic of Singapore
     Tien Y. Wong
106. Departments of Medicine/Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Republic of Singapore
     E-Shyong Tai
107. Office of Population Studies Foundation, University of San Carlos, Cebu City, 6000, Philippines
     Alan B. Feranil
108. Department of Anthropology, Northwestern University, Evanston, 60208, Illinois, USA
     Christopher W. Kuzawa
109. Department of Nutrition, Carolina Population Center, University of North Carolina, Chapel Hill, 27516, North Carolina, USA
     Linda S. Adair
110. Department of Medicine, University of Mississippi Medical Center, Jackson, 39126, Mississippi, USA
     Herman A. Taylor Jr & James G. Wilson
111. Children’s Hospital Oakland Research Institute, Oakland, 94609, California, USA
     Ronald M. Krauss
112. Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares, Madrid, 28029, Spain
     Jose M. Ordovas
113. Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Nutrition and Genomics Laboratory, Boston, 02111, Massachusetts, USA
     Jose M. Ordovas
114. Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.,
     Patricia B. Munroe
115. Sage Bionetworks, Seattle, 98109, Washington, USA
     Eric E. Schadt
116. Division of Community Health Sciences, St George’s University of London, London, SW17 0RE, UK
     David P. Strachan
117. Department of Cardiovascular Sciences, University of Leicester, NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, LE3 9QP, UK
     Nilesh J Samani

Authors

1. Tanya M. Teslovich
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2. Kiran Musunuru
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3. Albert V. Smith
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4. Andrew C. Edmondson
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5. Ioannis M. Stylianou
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6. Masahiro Koseki
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7. James P. Pirruccello
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8. Samuli Ripatti
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9. Daniel I. Chasman
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10. Cristen J. Willer
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11. Christopher T. Johansen
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12. Sigrid W. Fouchier
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13. Aaron Isaacs
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14. Gina M. Peloso
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15. Maja Barbalic
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16. Sally L. Ricketts
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17. Joshua C. Bis
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18. Yurii S. Aulchenko
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46. Robert Y. L. Zee
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48. Jacqueline C. M. Witteman
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50. Gonneke Willemsen
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51. H.-Erich Wichmann
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Contributions

T.M.T., K.M., A.V.S., A.C.E., I.M.S., M.K. and J.P.P. carried out the primary data analyses and/or experimental work. All other authors contributed to additional analyses. L.A.C., M.S.S., P.M.R., D.J.R., C.M.v.D., L.P., G.R.A., M.B. and S.K. conceived, designed, and supervised the study. K.M. wrote the manuscript.

Corresponding author

Correspondence toSekar Kathiresan.

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Competing interests

Competing interests: D.M.W., K.S. and V.M. are full-time employees of GlaxoSmithKline. M.S.S. has received research funding from GlaxoSmithKline. P.V. and G.W. received grant money from GlaxoSmithKline to fund the CoLaus study. G.T., K.S., U.T. and H.H. are full-time employees of deCODE genetics. The other authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, References, Supplementary Figures 1-3 with legends, Supplementary Tables 1-19 and a full list of Acknowledgments. (PDF 2944 kb)

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Teslovich, T., Musunuru, K., Smith, A. et al. Biological, clinical and population relevance of 95 loci for blood lipids.Nature 466, 707–713 (2010). https://doi.org/10.1038/nature09270

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• Received: 25 February 2010
• Accepted: 11 June 2010
• Issue Date: 05 August 2010
• DOI: https://doi.org/10.1038/nature09270