Discovery and refinement of loci associated with lipid levels

Nature Genetics - Tập 45 Số 11 - Trang 1274-1283 - 2013
Cristen J. Willer1,2,3,4, Ellen M. Schmidt2, Sebanti Sengupta1, Gina M. Peloso5,6,7, Stefan Gustafsson8,9, Stavroula Kanoni10, Andrea Ganna11,8,9, Ming‐Huei Chen1, Martin L. Buchkovich12, Samia Mora13,14, J. Beckmann15,16, Jennifer L. Bragg‐Gresham1, Hsing‐Yi Chang17, Ayşe Demirkan18, Heleen M. den Hertog19, Ron Do6, Louise A. Donnelly20, Georg Ehret21,22, Tõnu Esko5,23,24, Mary F. Feitosa25, Teresa Ferreira26, Krista Fischer23, Pierre Fontanillas5, Ross M. Fraser27, Daniel F. Freitag28, Deepti Gurdasani28,10, Kauko Heikkilä29, Elina Hyppönen30, Aaron Isaacs31,18, Anne Jackson1, Åsa Johansson32,33, Toby Johnson34,35, Marika Kaakinen36,37, Johannes Kettunen38,39, Marcus E. Kleber40,41, Xiaohui Li42, Jian’an Luan43, Leo‐Pekka Lyytikäinen44,45, Patrik K. E. Magnusson11, Massimo Mangino46, Reedik Mägi23,24, May E. Montasser47, Martina Müller‐Nurasyid48,49,50, Ilja M. Nolte51, Jeffrey R. O’Connell47, Cameron Palmer5,52,53, Markus Perola23,38,39, Ann Kristin Petersen49, Serena Sanna54, Richa Saxena55, Susan K. Service56, Sonia Shah57, Dmitry Shungin58,59,60, Carlo Sidore1,61,54, Ci Song11,8,9, Rona J. Strawbridge62,63, Ida Surakka38,39, Toshiko Tanaka64, Jan A. Staessen1, Guðmar Þorleifsson65, Evita G. van den Herik19, Benjamin F. Voight66,67, Kelly A. Volcik68, Lindsay L. Waite69, Andrew Wong70, Wei Xing Zheng12, Weihua Zhang71,72, Devin Absher69, Gershim Asiki73, Inês Barroso74,10, Latonya Been75, Jennifer L. Bolton27, Lori L. Bonnycastle76, Paolo Brambilla77, Mary Susan Burnett78, Giancarlo Cesana79, Maria Dimitriou80, Alex S. F. Doney20, Peter P. Pramstaller81,82, Paul Elliott83,37, Stephen E. Epstein78, Guðmundur I. Eyjólfsson84, Bruna Gigante85, Mark O. Goodarzi86, Harald Grallert87, Martha L Gravito75, Christopher G. Mathew88, Göran Hallmans89, Anna-Liisa Hartikainen90, Caroline Hayward91, Dena Hernández92, Andrew A. Hicks93, Hilma Hólm65, Yi-Jen Hung94, Thomas Meitinger95,87, Michelle R Jones86, Pontiano Kaleebu73, John J.P. Kastelein96, Kay-Tee Khaw97, Eric H. Kim42, Norman Klopp95,87, Pirjo Komulainen98, Meena Kumari57, Claudia Langenberg43, Terho Lehtimäki44,45, Shih-Yi Lin99, Jaana Lindström100, Ruth J. F. Loos43,101,102,103, François Mach21, Wendy L. McArdle104, Christa Meisinger81, Braxton D. Mitchell47, Gabrielle Müller105, Ramaiah Nagaraja106, Narisu Narisu76, Tuomo Nieminen107,108,109, Rebecca N. Nsubuga73, Ísleifur Ólafsson110, Ken K. Ong43,70, Aarno Palotie111,112,38, Theodore Papamarkou28,113,10, Cristina Pomilla28,10, Anneli Pouta90,114, Daniel J. Rader115,116, Muredach P. Reilly115,116, Paul M. Ridker13,14, Fernando Rivadeneira117,118,119, Igor Rudan27, Aimo Ruokonen120, Nilesh J. Samani121,122, Hubert Scharnagl123, Janet Seeley73,124, Kaisa Silander38,39, Alena Stančáková125, Kathleen Stirrups10, Amy J. Swift76, Laurence Tiret126, André G. Uitterlinden117,118,119, L. Joost van Pelt127,128, Sailaja Vedantam5,52,53, Nicholas W.J. Wainwright28,10, Cisca Wijmenga129,128, Sarah H. Wild27, Gonneke Willemsen130, Tom R. Gaunt131, James F. Wilson27, Elizabeth Young28,10, Jing Hua Zhao43, Linda S. Adair132, Dominique Arveiler133, Themistocles L. Assimes134, Stefania Bandinelli135, Franklyn I. Bennett136, Murielle Bochud137, Bernhard O. Boehm138,139, Dorret I. Boomsma130, Ingrid B. Borecki25, Stefan R. Bornstein140, Pascal Bovet137,141, Michel Burnier142, Harry Hemingway27, Aravinda Chakravarti22, John C. Chambers71,72,143, Yii-Der Ida Chen144,145, Francis S. Collins76, Richard Cooper146, John Danesh28, George Davey Smith80, Ulf dé Fairé85, Alan B. Feranil147, Jean Ferrières148, Luigi Ferrucci64, Nelson B. Freimer56,149, Christian Gieger49, Leif Groop150,151, Vilmundur Guðnason152, Ulf Gyllensten32, Anders Hamsten62,63,153, Tamara B. Harris154, Aroon D. Hingorani57, Joel N. Hirschhorn5,52,53, Albert Hofman117,119, G. Kees Hovingh96, Chao A. Hsiung155, Steve E. Humphries156, Steven E. Kahn157, Kristian Hveem158, Carlos Iribarren159, Marjo‐Riitta Järvelin36,83,37,114,160, Antti Jula161, Mika Kähönen162, Jaakko Kaprio163,29,38, Antero Kesäniemi164, Mika Kivimäki57, Jaspal S. Kooner72,143,165, Peter J. Koudstaal19, Ronald M. Krauss166, Diana Kuh70, Johan Auwerx167, Kirsten Ohm Kyvik168,169, Markku Laakso167, Timo A. Lakka170,98, Lars Lind171, Cecilia M. Lindgren26, Nicholas G. Martin172, Winfried März123,41,173, Mark I. McCarthy88,26, Colin A. Chapman174, Pierre Meneton175, Andres Metspalu23,24, Leena Moilanen176, Andrew P. Morris20, Patricia B. Munroe34,35, Inger Njølstad131, Nancy L. Pedersen11, Chris Power30, Jackie F. Price27, Bruce M. Psaty177,178, Thomas Quertermous134, Rainer Rauramaa179,98, Danish Saleheen180,181,28, Veikko Salomaa182, Dharambir K. Sanghera75, Jouko Saramies183, Peter E. H. Schwarz140,184, Wayne H.-H. Sheu185, Alan R. Shuldiner47,186, Agneta Siegbahn8,171,33, Tim D. Spector46, Kāri Stefánsson187,65, David P. Strachan188, Bamidele O. Tayo146, Elena Tremoli189, Jaakko Tuomilehto190,100,191,192, Matti Uusitupa193,194, Cornelia M. van Duijn31,18, Péter Vollenweider195, Lars Wallentin171,33, Nicholas J. Wareham43, John B. Whitfield172, Bruce H. R. Wolffenbuttel196,128, José M. Ordovás197,198,199, Eric Boerwinkle68, Colin N. A. Palmer20, Unnur Þorsteinsdóttir187,65, Daniel I. Chasman13,14, Jerome I. Rotter42, Paul W. Franks58,200,60, Samuli Ripatti38,39,10, L. Adrienne Cupples7,201, Manjinder S. Sandhu28,10, Stephen S. Rich202, Michael Boehnke1, Panos Deloukas10, Sekar Kathiresan5,203,6,204, Karen L. Mohlke12, Erik Ingelsson8,9,26, Gonçalo R. Abecasis1
1Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
3Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
4Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
5Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA.
6Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
7Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA.
8Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
9Science for Life Laboratory, Uppsala University, Uppsala, Sweden
10Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom.
11Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
12Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA.
13Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA.
14Harvard Medical School Boston, MA 02115 USA
15Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
16Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
17Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
18Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
19Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
20Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom.
21Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
22Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
23Estonian Genome Center of the University of Tartu, Tartu, Estonia.
24Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
25Department of Genetics, Washington University School of Medicine, USA
26Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom,
27Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland, United Kingdom
28Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
29Hjelt Institute, Department of Public Health, University of Helsinki, Finland
30Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom.
31Centre for Medical Systems Biology, Leiden, The Netherlands
32Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
33Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
34Clinical 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.
35Genome Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
36Biocenter Oulu, University of Oulu, Oulu, Finland
37Institute of Health Sciences, University of Oulu, Finland
38Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland
39Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
40Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany
41Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany
42Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
43MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom.
44Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland
45Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
46Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
47Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
48Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany
49Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
50Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany
51Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands
52Division of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA.
53Division of Genetics, Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA.
54Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, Italy.
55Massachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA.
56Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA.
57Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WC1E 6BT, United Kingdom.
58Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden.
59Department of Odontology, Umeå University, Umeå, Sweden
60Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden.
61Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy.
62Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
63Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
64Clinical Research Branch, National Institute Health, Baltimore, MD, USA.
65deCODE Genetics/Amgen, 101 Reykjavik, Iceland.
66Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA.
67Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA.
68Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA.
69HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA;
70MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom.
71Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
72Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom.
73MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
74University 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.
75Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK. USA
76Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
77Department of Experimental Medicine, University of Milano Bicocca, Italy.
78MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA
79Research Centre on Public Health, University of Milano Bicocca, Italy.
80Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece.
81Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany.
82Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany.
83Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK.
84The Laboratory in Mjodd, 108 Reykjavik, Iceland.
85Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
86Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
87Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
88Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, United Kingdom.
89Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Umeå, Sweden
90Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
91MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom.
92Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892 USA
93Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
94Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
95Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany.
96Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
97Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
98Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
99Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
100Diabetes Prevention Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland.
101The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at ount Sinai, New York, USA.
102The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA
103The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York.
104School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom
105Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
106Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA.
107Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew 33014, Finland.
108Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
109Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
110Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland.
111Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
112Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United ingdom.
113Department of Statistical Sciences, University College of London, London, United Kingdom.
114National Institute for Health and Welfare, Oulu, Finland
115Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA.
116Division 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.
117Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
118Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
119Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, The Netherlands.
120Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland.
121Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK
122National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK
123Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
124School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom
125University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
126INSERM UMRS 937, Pierre and Marie Curie University, Paris, France.
127Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands.
128LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands.
129Department of Genetics, University of Groningen, University Medical Center Groningen, the Netherlands
130Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands.
131Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
132Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
133Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France.
134Department of Medicine,, Stanford University School of Medicine, Stanford, CA USA
135Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy
136Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica.
137Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la corniche 10, 1010 Lausanne, Switzerland
138Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany.
139Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
140Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany
141Ministry of Health, Victoria, Republic of Seychelles
142Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland
143Imperial College Healthcare NHS Trust, London, United Kingdom
144Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
145Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
146Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA.
147Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines.
148Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
149Department of Psychiatry, University of California, Los Angeles, USA
150Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden.
151Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland.
152Icelandic Heart Association, Kopavogur, Iceland
153Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
154Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA.
155Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
156Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom.
157Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
158HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway
159Kaiser Permanente Division of Research, Oakland, CA, USA
160Unit of Primary Care, Oulu University Hospital, Oulu, Finland
161Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland
162Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland.
163Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
164Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland
165National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom.
166Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA.
167Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland
168Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark
169Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark
170Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland
171Department of Medical Sciences, Uppsala University, Uppsala, Sweden
172Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia.
173Synlab Academy, Synlab Services GmbH,Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany.
174Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona Kingston 7, Jamaica
175U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France.
176Department of Medicine, Kuopio University Hospital, Kuopio, Finland
177Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA
178Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA
179Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
180Center for Non-Communicable Diseases, Karachi, Pakistan
181Department of Medicine, University of Pennsylvania, USA
182Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland.
183South Karelia Central Hospital, Lappeenranta, Finland
184Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
185Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
186Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland
187Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland.
188Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
189Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy.
190Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria
191King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia.
192Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046.
193Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland
194Research Unit, Kuopio University Hospital, Kuopio, Finland
195Department of Medicine, Lausanne University Hospital, Switzerland.
196Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands
197Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain.
198IMDEA-Alimentacion, Madrid, Spain
199Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
200Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
201Framingham Heart Study, Framingham, MA, USA
202Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
203Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
204Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA

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Tài liệu tham khảo

Kannel, W.B., Dawber, T.R., Kagan, A., Revotskie, N. & Stokes, J. III. Factors of risk in the development of coronary heart disease—six year follow-up experience. The Framingham Study. Ann. Intern. Med. 55, 33–50 (1961).

Castelli, W.P. Cholesterol and lipids in the risk of coronary artery disease—the Framingham Heart Study. Can. J. Cardiol. 4 (suppl. A), 5A–10A (1988).

Lloyd-Jones, D. et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation 121, e46–e215 (2010).

Teslovich, T.M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707–713 (2010).

Barter, P.J. & Rye, K.A. Cholesteryl ester transfer protein (CETP) inhibition as a strategy to reduce cardiovascular risk. J. Lipid Res. 53, 1755–1766 (2012).

Rahalkar, A.R. & Hegele, R.A. Monogenic pediatric dyslipidemias: classification, genetics and clinical spectrum. Mol. Genet. Metab. 93, 282–294 (2008).

Musunuru, K. et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466, 714–719 (2010).

Voight, B.F. et al. The Metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits. PLoS Genet. 8, e1002793 (2012).

1000 Genomes Project Consortium. A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 (2010).

Sanna, S. et al. Fine mapping of five loci associated with low-density lipoprotein cholesterol detects variants that double the explained heritability. PLoS Genet. 7, e1002198 (2011).

Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997–1004 (1999).

Asselbergs, F.W. et al. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci. Am. J. Hum. Genet. 91, 823–838 (2012).

Welch, C.L. et al. Genetic regulation of cholesterol homeostasis: chromosomal organization of candidate genes. J. Lipid Res. 37, 1406–1421 (1996).

Sarria, A.J., Panini, S.R. & Evans, R.M. A functional role for vimentin intermediate filaments in the metabolism of lipoprotein-derived cholesterol in human SW-13 cells. J. Biol. Chem. 267, 19455–19463 (1992).

Hagberg, C.E. et al. Vascular endothelial growth factor B controls endothelial fatty acid uptake. Nature 464, 917–921 (2010).

Ashburner, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25–29 (2000).

Segrè, A.V., Groop, L., Mootha, V.K., Daly, M.J. & Altshuler, D. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 6, e1001058 (2010).

Fitzgerald, M.L., Moore, K.J. & Freeman, M.W. Nuclear hormone receptors and cholesterol trafficking: the orphans find a new home. J. Mol. Med. (Berl.) 80, 271–281 (2002).

Rossin, E.J. et al. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet. 7, e1001273 (2011).

Plyte, S.E., Hughes, K., Nikolakaki, E., Pulverer, B.J. & Woodgett, J.R. Glycogen synthase kinase-3: functions in oncogenesis and development. Biochim. Biophys. Acta 1114, 147–162 (1992).

Toker, A. & Cantley, L.C. Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 387, 673–676 (1997).

Kaprio, J., Ferrell, R.E., Kottke, B.A., Kamboh, M.I. & Sing, C.F. Effects of polymorphisms in apolipoproteins E, A-IV, and H on quantitative traits related to risk for cardiovascular disease. Arterioscler. Thromb. 11, 1330–1348 (1991).

Ernst, J. et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473, 43–49 (2011).

The ENCODE Project Consortium. A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol. 9, e1001046 (2011).

Buyske, S. et al. Evaluation of the metabochip genotyping array in African Americans and implications for fine mapping of GWAS-identified loci: the PAGE study. PLoS ONE 7, e35651 (2012).

Palmen, J. et al. The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA52, and their paradoxical association with plasma triglyceride but not plasma apoAV levels. Biochim. Biophys. Acta 1782, 447–452 (2008).

Schunkert, H. et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 43, 333–338 (2011).

Coronary Artery Disease (C4D) Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat. Genet. 43, 339–344 (2011).

Voight, B.F. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet. 42, 579–589 (2010).

Speliotes, E.K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937–948 (2010).

Heid, I.M. et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat. Genet. 42, 949–960 (2010).

Ehret, G.B. et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103–109 (2011).

Dupuis, J. et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet. 42, 105–116 (2010).

Freathy, R.M. et al. Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI. Diabetes 57, 1419–1426 (2008).

Clarke, R. et al. Cholesterol fractions and apolipoproteins as risk factors for heart disease mortality in older men. Arch. Intern. Med. 167, 1373–1378 (2007).

Willer, C.J. et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet. 40, 161–169 (2008).

Voight, B.F. et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 380, 572–580 (2012).

Frikke-Schmidt, R. et al. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. J. Am. Med. Assoc. 299, 2524–2532 (2008).

Do, R. et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat. Genet. doi:10.1038/ng.2795 (6 October 2013).10.1038/ng.2795

Demirkan, A. et al. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. PLoS Genet. 8, e1002490 (2012).

Friedewald, W.T., Levy, R.I. & Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502 (1972).

Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).

Kang, H.M. et al. Variance component model to account for sample structure in genome-wide association studies. Nat. Genet. 42, 348–354 (2010).

Stouffer, S.A., Suchman, E.A., DeVinney, L.C., Star, S.A. & Williams, R.M.J. Adjustment During Army Life (Princeton University Press, Princeton, NJ., 1949).

Willer, C.J., Li, Y. & Abecasis, G.R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).

Keating, B.J. et al. Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies. PLoS ONE 3, e3583 (2008).

Schadt, E.E. et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 6, e107 (2008).

Chasman, D.I. et al. Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis. PLoS Genet. 5, e1000730 (2009).

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Nature Genetics

Tập 45 Số 11

1274-1283

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