Discovery and refinement of loci associated with lipid levels

doi:10.1038/ng.2797

. 2013 Nov;45(11):1274-1283.

doi: 10.1038/ng.2797. Epub 2013 Oct 6.

Discovery and refinement of loci associated with lipid levels

Cristen J Willer^#^{1

2

3

4}, Ellen M Schmidt^#², Sebanti Sengupta^#⁴, Gina M Peloso^{5

6

7}, Stefan Gustafsson^{8

9}, Stavroula Kanoni¹⁰, Andrea Ganna^{8

9

11}, Jin Chen⁴, Martin L Buchkovich¹², Samia Mora^{13

14}, Jacques S Beckmann^{15

16}, Jennifer L Bragg-Gresham⁴, Hsing-Yi Chang¹⁷, Ayşe Demirkan¹⁸, Heleen M Den Hertog¹⁹, Ron Do⁶, Louise A Donnelly²⁰, Georg B Ehret^{21

22}, Tõnu Esko^{7

23

24}, Mary F Feitosa²⁵, Teresa Ferreira²⁶, Krista Fischer²³, Pierre Fontanillas⁷, Ross M Fraser²⁷, Daniel F Freitag²⁸, Deepti Gurdasani^{10

28}, Kauko Heikkilä²⁹, Elina Hyppönen³⁰, Aaron Isaacs^{18

31}, Anne U Jackson⁴, Åsa Johansson^{32

33}, Toby Johnson^{34

35}, Marika Kaakinen^{36

37}, Johannes Kettunen^{38

39}, Marcus E Kleber^{40

41}, Xiaohui Li⁴², Jian'an Luan⁴³, Leo-Pekka Lyytikäinen^{44

45}, Patrik K E Magnusson¹¹, Massimo Mangino⁴⁶, Evelin Mihailov^{23

24}, May E Montasser⁴⁷, Martina Müller-Nurasyid^{48

49

50}, Ilja M Nolte⁵¹, Jeffrey R O'Connell⁴⁷, Cameron D Palmer^{7

52

53}, Markus Perola^{23

38

39}, Ann-Kristin Petersen⁴⁸, Serena Sanna⁵⁴, Richa Saxena⁵⁵, Susan K Service⁵⁶, Sonia Shah⁵⁷, Dmitry Shungin^{58

59

60}, Carlo Sidore^{4

54

61}, Ci Song^{8

9

11}, Rona J Strawbridge^{62

63}, Ida Surakka^{38

39}, Toshiko Tanaka⁶⁴, Tanya M Teslovich⁴, Gudmar Thorleifsson⁶⁵, Evita G Van den Herik¹⁹, Benjamin F Voight^{66

67}, Kelly A Volcik⁶⁸, Lindsay L Waite⁶⁹, Andrew Wong⁷⁰, Ying Wu¹², Weihua Zhang^{71

72}, Devin Absher⁶⁹, Gershim Asiki⁷³, Inês Barroso^{10

74}, Latonya F Been⁷⁵, Jennifer L Bolton²⁷, Lori L Bonnycastle⁷⁶, Paolo Brambilla⁷⁷, Mary S Burnett⁷⁸, Giancarlo Cesana⁷⁹, Maria Dimitriou⁸⁰, Alex S F Doney²⁰, Angela Döring^{81

82}, Paul Elliott^{37

83}, Stephen E Epstein⁷⁸, Gudmundur Ingi Eyjolfsson⁸⁴, Bruna Gigante⁸⁵, Mark O Goodarzi⁸⁶, Harald Grallert⁸⁷, Martha L Gravito⁷⁵, Christopher J Groves⁸⁸, Göran Hallmans⁸⁹, Anna-Liisa Hartikainen⁹⁰, Caroline Hayward⁹¹, Dena Hernandez⁹², Andrew A Hicks⁹³, Hilma Holm⁶⁵, Yi-Jen Hung⁹⁴, Thomas Illig^{87

95}, Michelle R Jones⁸⁶, Pontiano Kaleebu⁷³, John J P Kastelein⁹⁶, Kay-Tee Khaw⁹⁷, Eric Kim⁴², Norman Klopp^{87

95}, Pirjo Komulainen⁹⁸, Meena Kumari⁵⁷, Claudia Langenberg⁴³, Terho Lehtimäki^{44

45}, Shih-Yi Lin⁹⁹, Jaana Lindström¹⁰⁰, Ruth J F Loos^{43

101

102

103}, François Mach²¹, Wendy L McArdle¹⁰⁴, Christa Meisinger⁸¹, Braxton D Mitchell⁴⁷, Gabrielle Müller¹⁰⁵, Ramaiah Nagaraja¹⁰⁶, Narisu Narisu⁷⁶, Tuomo V M Nieminen^{107

108

109}, Rebecca N Nsubuga⁷³, Isleifur Olafsson¹¹⁰, Ken K Ong^{43

70}, Aarno Palotie^{38

111

112}, Theodore Papamarkou^{10

28

113}, Cristina Pomilla^{10

28}, Anneli Pouta^{90

114}, Daniel J Rader^{115

116}, Muredach P Reilly^{115

116}, Paul M Ridker^{13

14}, Fernando Rivadeneira^{117

118

119}, Igor Rudan²⁷, Aimo Ruokonen¹²⁰, Nilesh Samani^{121

122}, Hubert Scharnagl¹²³, Janet Seeley^{73

124}, Kaisa Silander^{38

39}, Alena Stančáková¹²⁵, Kathleen Stirrups¹⁰, Amy J Swift⁷⁶, Laurence Tiret¹²⁶, Andre G Uitterlinden^{117

118

119}, L Joost van Pelt^{127

128}, Sailaja Vedantam^{7

52

53}, Nicholas Wainwright^{10

28}, Cisca Wijmenga^{128

129}, Sarah H Wild²⁷, Gonneke Willemsen¹³⁰, Tom Wilsgaard¹³¹, James F Wilson²⁷, Elizabeth H Young^{10

28}, Jing Hua Zhao⁴³, Linda S Adair¹³², Dominique Arveiler¹³³, Themistocles L Assimes¹³⁴, Stefania Bandinelli¹³⁵, Franklyn Bennett¹³⁶, Murielle Bochud¹³⁷, Bernhard O Boehm^{138

139}, Dorret I Boomsma¹³⁰, Ingrid B Borecki²⁵, Stefan R Bornstein¹⁴⁰, Pascal Bovet^{137

141}, Michel Burnier¹⁴², Harry Campbell²⁷, Aravinda Chakravarti²², John C Chambers^{71

72

143}, Yii-Der Ida Chen^{144

145}, Francis S Collins⁷⁶, Richard S Cooper¹⁴⁶, John Danesh²⁸, George Dedoussis⁸⁰, Ulf de Faire⁸⁵, Alan B Feranil¹⁴⁷, Jean Ferrières¹⁴⁸, Luigi Ferrucci⁶⁴, Nelson B Freimer^{56

149}, Christian Gieger⁴⁸, Leif C Groop^{150

151}, Vilmundur Gudnason¹⁵², Ulf Gyllensten³², Anders Hamsten^{62

63

153}, Tamara B Harris¹⁵⁴, Aroon Hingorani⁵⁷, Joel N Hirschhorn^{7

52

53}, Albert Hofman^{117

119}, G Kees Hovingh⁹⁶, Chao Agnes Hsiung¹⁵⁵, Steve E Humphries¹⁵⁶, Steven C Hunt¹⁵⁷, Kristian Hveem¹⁵⁸, Carlos Iribarren¹⁵⁹, Marjo-Riitta Järvelin^{36

37

83

114

160}, Antti Jula¹⁶¹, Mika Kähönen¹⁶², Jaakko Kaprio^{29

38

163}, Antero Kesäniemi¹⁶⁴, Mika Kivimaki⁵⁷, Jaspal S Kooner^{72

143

165}, Peter J Koudstaal¹⁹, Ronald M Krauss¹⁶⁶, Diana Kuh⁷⁰, Johanna Kuusisto¹⁶⁷, Kirsten O Kyvik^{168

169}, Markku Laakso¹⁶⁷, Timo A Lakka^{98

170}, Lars Lind¹⁷¹, Cecilia M Lindgren²⁶, Nicholas G Martin¹⁷², Winfried März^{41

123

173}, Mark I McCarthy^{26

88}, Colin A McKenzie¹⁷⁴, Pierre Meneton¹⁷⁵, Andres Metspalu^{23

24}, Leena Moilanen¹⁷⁶, Andrew D Morris²⁰, Patricia B Munroe^{34

35}, Inger Njølstad¹³¹, Nancy L Pedersen¹¹, Chris Power³⁰, Peter P Pramstaller^{93

177

178}, Jackie F Price²⁷, Bruce M Psaty^{179

180}, Thomas Quertermous¹³⁴, Rainer Rauramaa^{98

181}, Danish Saleheen^{28

182

183}, Veikko Salomaa¹⁸⁴, Dharambir K Sanghera⁷⁵, Jouko Saramies¹⁸⁵, Peter E H Schwarz^{140

186}, Wayne H-H Sheu¹⁸⁷, Alan R Shuldiner^{47

188}, Agneta Siegbahn^{8

33

171}, Tim D Spector⁴⁶, Kari Stefansson^{65

189}, David P Strachan¹⁹⁰, Bamidele O Tayo¹⁴⁶, Elena Tremoli¹⁹¹, Jaakko Tuomilehto^{100

192

193

194}, Matti Uusitupa^{195

196}, Cornelia M van Duijn^{18

31}, Peter Vollenweider¹⁹⁷, Lars Wallentin^{33

171}, Nicholas J Wareham⁴³, John B Whitfield¹⁷², Bruce H R Wolffenbuttel^{128

198}, Jose M Ordovas^{199

200

201}, Eric Boerwinkle⁶⁸, Colin N A Palmer²⁰, Unnur Thorsteinsdottir^{65

189}, Daniel I Chasman^{13

14}, Jerome I Rotter⁴², Paul W Franks^{58

60

202}, Samuli Ripatti^{10

38

39}, L Adrienne Cupples^{5

203}, Manjinder S Sandhu^{10

28}, Stephen S Rich²⁰⁴, Michael Boehnke^#⁴, Panos Deloukas^#¹⁰, Sekar Kathiresan^#^{6

7

205

206}, Karen L Mohlke^#¹², Erik Ingelsson^#^{8

9

26}, Gonçalo R Abecasis^#⁴; Global Lipids Genetics Consortium

Affiliations

¹ Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
² Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
³ Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁴ Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁵ Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
⁶ Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
⁷ Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA.
⁸ Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
⁹ Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁰ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom.
¹¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹² Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA.
¹³ Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA.
¹⁴ Harvard Medical School, Boston MA 02115, USA.
¹⁵ Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland.
¹⁶ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
¹⁷ Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
¹⁸ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁹ Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
²⁰ Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom.
²¹ Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
²² Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
²³ Estonian Genome Center of the University of Tartu, Tartu, Estonia.
²⁴ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
²⁵ Department of Genetics, Washington University School of Medicine, USA.
²⁶ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
²⁷ Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, United Kingdom.
²⁸ Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
²⁹ Hjelt Institute, Department of Public Health, University of Helsinki, Finland.
³⁰ Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom.
³¹ Centre for Medical Systems Biology, Leiden, the Netherlands.
³² Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
³³ Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
³⁴ Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³⁵ Clinical Pharmacology, NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London, London, UK.
³⁶ Biocenter Oulu, University of Oulu, Oulu, Finland.
³⁷ Institute of Health Sciences, University of Oulu, Finland.
³⁸ Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland.
³⁹ Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
⁴⁰ Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany.
⁴¹ Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany.
⁴² Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁴³ MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
⁴⁴ Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland.
⁴⁵ Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
⁴⁶ Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
⁴⁷ Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland.
⁴⁸ Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁴⁹ Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany.
⁵⁰ Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany.
⁵¹ Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
⁵² Division of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA.
⁵³ Division of Genetics, Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA.
⁵⁴ Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, Italy.
⁵⁵ Massachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA.
⁵⁶ Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
⁵⁷ Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WC1E 6BT, United Kingdom.
⁵⁸ Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden.
⁵⁹ Department of Odontology, Umeå University, Umeå, Sweden.
⁶⁰ Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden.
⁶¹ Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy.
⁶² Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
⁶³ Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
⁶⁴ Clinical Research Branch, National Institute Health, Baltimore, MD, USA.
⁶⁵ deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
⁶⁶ Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA.
⁶⁷ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA.
⁶⁸ Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA.
⁶⁹ HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
⁷⁰ MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom.
⁷¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
⁷² Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom.
⁷³ MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
⁷⁴ University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK.
⁷⁵ Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁷⁶ Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷⁷ Department of Experimental Medicine, University of Milano Bicocca, Italy.
⁷⁸ MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA.
⁷⁹ Research Centre on Public Health, University of Milano Bicocca, Italy.
⁸⁰ Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece.
⁸¹ Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸² Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸³ Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK.
⁸⁴ The Laboratory in Mjodd, 108 Reykjavik, Iceland.
⁸⁵ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁸⁶ Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁸⁷ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸⁸ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, United Kingdom.
⁸⁹ Department of Public Health and Clinical Medicine, Nutritional research, Umeå University, Umeå, Sweden.
⁹⁰ Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
⁹¹ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom.
⁹² Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
⁹³ Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
⁹⁴ Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁹⁵ Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany.
⁹⁶ Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
⁹⁷ Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
⁹⁸ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
⁹⁹ Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹⁰⁰ Diabetes Prevention Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland.
¹⁰¹ The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁰² The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at ount Sinai, New York, USA.
¹⁰³ The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York.
¹⁰⁴ School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
¹⁰⁵ Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
¹⁰⁶ Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA.
¹⁰⁷ Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew 33014, Finland.
¹⁰⁸ Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland.
¹⁰⁹ Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
¹¹⁰ Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland.
¹¹¹ Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
¹¹² Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United ingdom.
¹¹³ Department of Statistical Sciences, University College of London, London, United Kingdom.
¹¹⁴ National Institute for Health and Welfare, Oulu, Finland.
¹¹⁵ Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA.
¹¹⁶ Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA.
¹¹⁷ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹¹⁸ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹¹⁹ Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, The Netherlands.
¹²⁰ Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland.
¹²¹ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
¹²² Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK.
¹²³ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
¹²⁴ School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
¹²⁵ University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
¹²⁶ INSERM UMRS 937, Pierre and Marie Curie University, Paris, France.
¹²⁷ Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.
¹²⁸ LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands.
¹²⁹ Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
¹³⁰ Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands.
¹³¹ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
¹³² Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
¹³³ Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France.
¹³⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹³⁵ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
¹³⁶ Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica.
¹³⁷ Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland.
¹³⁸ Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany.
¹³⁹ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
¹⁴⁰ Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
¹⁴¹ Ministry of Health, Victoria, Republic of Seychelles.
¹⁴² Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland.
¹⁴³ Imperial College Healthcare NHS Trust, London, United Kingdom.
¹⁴⁴ Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
¹⁴⁵ Department of Medicine, University of California Los Angeles, Los Angeles, California, USA.
¹⁴⁶ Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA.
¹⁴⁷ Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines.
¹⁴⁸ Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France.
¹⁴⁹ Department of Psychiatry, University of California, Los Angeles, USA.
¹⁵⁰ Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden.
¹⁵¹ Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland.
¹⁵² Icelandic Heart Association, Kopavogur, Iceland.
¹⁵³ Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
¹⁵⁴ Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA.
¹⁵⁵ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
¹⁵⁶ Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom.
¹⁵⁷ Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹⁵⁸ HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
¹⁵⁹ Kaiser Permanente, Division of Research, Oakland, CA, USA.
¹⁶⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
¹⁶¹ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.
¹⁶² Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland.
¹⁶³ Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
¹⁶⁴ Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
¹⁶⁵ National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom.
¹⁶⁶ Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA.
¹⁶⁷ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
¹⁶⁸ Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
¹⁶⁹ Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
¹⁷⁰ Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland.
¹⁷¹ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁷² Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia.
¹⁷³ Synlab Academy, Synlab Services GmbH,Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany.
¹⁷⁴ Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
¹⁷⁵ U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France.
¹⁷⁶ Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁷⁷ Department of Neurology, General Central Hospital, Bolzano, Italy.
¹⁷⁸ Department of Neurology, University of Lübeck, Lübeck, Germany.
¹⁷⁹ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
¹⁸⁰ Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
¹⁸¹ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁸² Center for Non-Communicable Diseases, Karachi, Pakistan.
¹⁸³ Department of Medicine, University of Pennsylvania, USA.
¹⁸⁴ Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland.
¹⁸⁵ South Karelia Central Hospital, Lappeenranta, Finland.
¹⁸⁶ Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany.
¹⁸⁷ Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁸⁸ Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland.
¹⁸⁹ Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland.
¹⁹⁰ Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
¹⁹¹ Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy.
¹⁹² Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria.
¹⁹³ King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia.
¹⁹⁴ Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046.
¹⁹⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
¹⁹⁶ Research Unit, Kuopio University Hospital, Kuopio, Finland.
¹⁹⁷ Department of Medicine, Lausanne University Hospital, Switzerland.
¹⁹⁸ Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands.
¹⁹⁹ Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain.
²⁰⁰ IMDEA-Alimentacion, Madrid, Spain.
²⁰¹ Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
²⁰² Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
²⁰³ Framingham Heart Study, Framingham, MA, USA.
²⁰⁴ Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
²⁰⁵ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
²⁰⁶ Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

^# Contributed equally.

PMID: 24097068
PMCID: PMC3838666
DOI: 10.1038/ng.2797

Discovery and refinement of loci associated with lipid levels

Cristen J Willer et al. Nat Genet. 2013 Nov.

. 2013 Nov;45(11):1274-1283.

doi: 10.1038/ng.2797. Epub 2013 Oct 6.

Authors

Affiliations

¹ Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
² Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
³ Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁴ Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁵ Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
⁶ Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
⁷ Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA.
⁸ Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
⁹ Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁰ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom.
¹¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹² Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA.
¹³ Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA.
¹⁴ Harvard Medical School, Boston MA 02115, USA.
¹⁵ Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland.
¹⁶ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
¹⁷ Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
¹⁸ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁹ Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands.
²⁰ Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom.
²¹ Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
²² Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
²³ Estonian Genome Center of the University of Tartu, Tartu, Estonia.
²⁴ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
²⁵ Department of Genetics, Washington University School of Medicine, USA.
²⁶ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.
²⁷ Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, United Kingdom.
²⁸ Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
²⁹ Hjelt Institute, Department of Public Health, University of Helsinki, Finland.
³⁰ Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom.
³¹ Centre for Medical Systems Biology, Leiden, the Netherlands.
³² Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
³³ Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
³⁴ Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³⁵ Clinical Pharmacology, NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London, London, UK.
³⁶ Biocenter Oulu, University of Oulu, Oulu, Finland.
³⁷ Institute of Health Sciences, University of Oulu, Finland.
³⁸ Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland.
³⁹ Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland.
⁴⁰ Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany.
⁴¹ Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany.
⁴² Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁴³ MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
⁴⁴ Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland.
⁴⁵ Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
⁴⁶ Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.
⁴⁷ Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland.
⁴⁸ Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁴⁹ Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany.
⁵⁰ Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany.
⁵¹ Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands.
⁵² Division of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA.
⁵³ Division of Genetics, Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA.
⁵⁴ Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, Italy.
⁵⁵ Massachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA.
⁵⁶ Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
⁵⁷ Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WC1E 6BT, United Kingdom.
⁵⁸ Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden.
⁵⁹ Department of Odontology, Umeå University, Umeå, Sweden.
⁶⁰ Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden.
⁶¹ Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy.
⁶² Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
⁶³ Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
⁶⁴ Clinical Research Branch, National Institute Health, Baltimore, MD, USA.
⁶⁵ deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
⁶⁶ Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA.
⁶⁷ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA.
⁶⁸ Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA.
⁶⁹ HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
⁷⁰ MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom.
⁷¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
⁷² Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom.
⁷³ MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
⁷⁴ University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK.
⁷⁵ Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁷⁶ Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷⁷ Department of Experimental Medicine, University of Milano Bicocca, Italy.
⁷⁸ MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA.
⁷⁹ Research Centre on Public Health, University of Milano Bicocca, Italy.
⁸⁰ Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece.
⁸¹ Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸² Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸³ Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK.
⁸⁴ The Laboratory in Mjodd, 108 Reykjavik, Iceland.
⁸⁵ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁸⁶ Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
⁸⁷ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸⁸ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, United Kingdom.
⁸⁹ Department of Public Health and Clinical Medicine, Nutritional research, Umeå University, Umeå, Sweden.
⁹⁰ Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
⁹¹ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom.
⁹² Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.
⁹³ Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
⁹⁴ Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁹⁵ Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany.
⁹⁶ Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
⁹⁷ Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
⁹⁸ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
⁹⁹ Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹⁰⁰ Diabetes Prevention Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland.
¹⁰¹ The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA.
¹⁰² The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at ount Sinai, New York, USA.
¹⁰³ The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York.
¹⁰⁴ School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom.
¹⁰⁵ Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
¹⁰⁶ Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA.
¹⁰⁷ Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew 33014, Finland.
¹⁰⁸ Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland.
¹⁰⁹ Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.
¹¹⁰ Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland.
¹¹¹ Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
¹¹² Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United ingdom.
¹¹³ Department of Statistical Sciences, University College of London, London, United Kingdom.
¹¹⁴ National Institute for Health and Welfare, Oulu, Finland.
¹¹⁵ Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA.
¹¹⁶ Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA.
¹¹⁷ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹¹⁸ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
¹¹⁹ Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, The Netherlands.
¹²⁰ Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland.
¹²¹ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
¹²² Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK.
¹²³ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
¹²⁴ School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom.
¹²⁵ University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
¹²⁶ INSERM UMRS 937, Pierre and Marie Curie University, Paris, France.
¹²⁷ Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.
¹²⁸ LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands.
¹²⁹ Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
¹³⁰ Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands.
¹³¹ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
¹³² Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
¹³³ Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France.
¹³⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
¹³⁵ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
¹³⁶ Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica.
¹³⁷ Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland.
¹³⁸ Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany.
¹³⁹ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
¹⁴⁰ Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
¹⁴¹ Ministry of Health, Victoria, Republic of Seychelles.
¹⁴² Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland.
¹⁴³ Imperial College Healthcare NHS Trust, London, United Kingdom.
¹⁴⁴ Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
¹⁴⁵ Department of Medicine, University of California Los Angeles, Los Angeles, California, USA.
¹⁴⁶ Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA.
¹⁴⁷ Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines.
¹⁴⁸ Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France.
¹⁴⁹ Department of Psychiatry, University of California, Los Angeles, USA.
¹⁵⁰ Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden.
¹⁵¹ Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland.
¹⁵² Icelandic Heart Association, Kopavogur, Iceland.
¹⁵³ Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
¹⁵⁴ Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA.
¹⁵⁵ Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
¹⁵⁶ Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom.
¹⁵⁷ Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹⁵⁸ HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
¹⁵⁹ Kaiser Permanente, Division of Research, Oakland, CA, USA.
¹⁶⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
¹⁶¹ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland.
¹⁶² Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland.
¹⁶³ Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
¹⁶⁴ Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
¹⁶⁵ National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom.
¹⁶⁶ Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA.
¹⁶⁷ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
¹⁶⁸ Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
¹⁶⁹ Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
¹⁷⁰ Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland.
¹⁷¹ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
¹⁷² Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia.
¹⁷³ Synlab Academy, Synlab Services GmbH,Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany.
¹⁷⁴ Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
¹⁷⁵ U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France.
¹⁷⁶ Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁷⁷ Department of Neurology, General Central Hospital, Bolzano, Italy.
¹⁷⁸ Department of Neurology, University of Lübeck, Lübeck, Germany.
¹⁷⁹ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA.
¹⁸⁰ Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
¹⁸¹ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁸² Center for Non-Communicable Diseases, Karachi, Pakistan.
¹⁸³ Department of Medicine, University of Pennsylvania, USA.
¹⁸⁴ Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland.
¹⁸⁵ South Karelia Central Hospital, Lappeenranta, Finland.
¹⁸⁶ Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany.
¹⁸⁷ Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁸⁸ Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland.
¹⁸⁹ Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland.
¹⁹⁰ Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
¹⁹¹ Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy.
¹⁹² Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria.
¹⁹³ King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia.
¹⁹⁴ Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046.
¹⁹⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
¹⁹⁶ Research Unit, Kuopio University Hospital, Kuopio, Finland.
¹⁹⁷ Department of Medicine, Lausanne University Hospital, Switzerland.
¹⁹⁸ Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands.
¹⁹⁹ Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain.
²⁰⁰ IMDEA-Alimentacion, Madrid, Spain.
²⁰¹ Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
²⁰² Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
²⁰³ Framingham Heart Study, Framingham, MA, USA.
²⁰⁴ Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
²⁰⁵ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
²⁰⁶ Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

^# Contributed equally.

PMID: 24097068
PMCID: PMC3838666
DOI: 10.1038/ng.2797

Abstract

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

PubMed Disclaimer

Figures

**FIGURE 1. Overlap between loci associated with different lipid traits**
This Venn Diagram illustrates the number of loci that show association with multiple lipid traits. The number of loci primarily associated with only one trait is listed in parentheses after the trait name and the locus name is listed below in italics. Loci that show association with two or more traits are shown in the appropriate section.

See this image and copyright information in PMC

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References

1. Kannel WB, Dawber TR, Kagan A, Revotskie N, Stokes J., 3rd Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. Annals of Internal Medicine. 1961;55:33–50. - PubMed
1. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study. Canadian Journal of Cardiology. 1988;4(Suppl A):5A–10A. - PubMed
1. Lloyd-Jones D, et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–e215. - PubMed
1. Teslovich TM, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13. - PMC - PubMed
1. Barter PJ, Rye KA. Cholesteryl ester transfer protein (CETP) inhibition as a strategy to reduce cardiovascular isk. Journal of Lipid Research. 2012 - PMC - PubMed

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[1] Kannel WB, Dawber TR, Kagan A, Revotskie N, Stokes J., 3rd Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. Annals of Internal Medicine. 1961;55:33–50. - PubMed

[2] Kannel WB, Dawber TR, Kagan A, Revotskie N, Stokes J., 3rd Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. Annals of Internal Medicine. 1961;55:33–50. - PubMed

[3] Castelli WP. Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study. Canadian Journal of Cardiology. 1988;4(Suppl A):5A–10A. - PubMed

[4] Castelli WP. Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study. Canadian Journal of Cardiology. 1988;4(Suppl A):5A–10A. - PubMed

[5] Lloyd-Jones D, et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–e215. - PubMed

[6] Lloyd-Jones D, et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–e215. - PubMed

[7] Teslovich TM, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13. - PMC - PubMed

[8] Teslovich TM, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13. - PMC - PubMed

[9] Barter PJ, Rye KA. Cholesteryl ester transfer protein (CETP) inhibition as a strategy to reduce cardiovascular isk. Journal of Lipid Research. 2012 - PMC - PubMed

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Discovery and refinement of loci associated with lipid levels

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Discovery and refinement of loci associated with lipid levels

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