Discovery and refinement of loci associated with lipid levels.
Journal: Nature genetics
Volume: 45
Issue: 11
Year of Publication: 2014
Affiliated Institutions: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan , USA. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan , USA. Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan , USA. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts , USA. Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB SA, Hinxton, United Kingdom. Department of Genetics, University of North Carolina, Chapel Hill, NC USA. Division of Preventive Medicine, Brigham and Women's Hospital, Commonwealth Ave., Boston MA , USA. Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland. Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts , USA. Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD SY, United Kingdom. Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil , Geneva , Switzerland. Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts , USA. Department of Genetics, Washington University School of Medicine, USA. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX BN, United Kingdom. Estonian Genome Center of the University of Tartu, Tartu, Estonia. Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH AG, Scotland, United Kingdom. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. Hjelt Institute, Department of Public Health, University of Helsinki, Finland. Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Biocenter Oulu, University of Oulu, Oulu, Finland. Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland. Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA , USA. MRC Epidemiology Unit, Institute of Metabolic Science, Box , Addenbrooke's Hospital, Hills Road, Cambridge, CB QQ, United Kingdom. Department of Clinical Chemistry, Fimlab Laboratories, Tampere , Finland. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom. Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland. Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg , Germany. Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands. Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, , Italy. Massachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA. Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA. Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WCE BT, United Kingdom. Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden. Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. Clinical Research Branch, National Institute Health, Baltimore, MD, USA. deCODE Genetics/Amgen, Reykjavik, Iceland. Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, , USA. Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX , USA. HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA. MRC Unit for Lifelong Health and Ageing, Bedford Place, London, WCB JU, United Kingdom. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD , USA. Department of Experimental Medicine, University of Milano Bicocca, Italy. MedStar Health Research Institute, Belcrest Road, Suite , Hyattsville, MD , USA. Research Centre on Public Health, University of Milano Bicocca, Italy. Department of Dietetics-Nutrition, Harokopio University, El. Venizelou Str, Athens, Greece. Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg , Germany. Institute of Health Sciences, University of Oulu, Finland. The Laboratory in Mjodd, Reykjavik, Iceland. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA , USA. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg , Germany. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX LJ, United Kingdom. Department of Public Health and Clinical Medicine, Nutritional research, Umeå University, Umeå, Sweden. Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD , USA. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany. Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom. Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland. School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS BN, United Kingdom. Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse , Dresden, Germany. Laboratory of Genetics, National Institute on Aging, Baltimore, MD, USA. Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew , Finland. Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland. Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Civic Center Blvd, Building , Translational Research Center, Philadelphia, PA -, USA. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland. National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE QP, UK. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. INSERM UMRS , Pierre and Marie Curie University, Paris, France. Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands. LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands. Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA. Department of Epidemiology and Public Health, EA , University of Strasbourg, Faculty of Medicine, Strasbourg, France. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy. Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston , Jamaica. Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche , Lausanne, Switzerland. Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany. Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse , Dresden, Germany. Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland. Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD , USA. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA. Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois , USA. Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines. Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France. Department of Clinical Sciences, Lund University, SE-, Malmö, Sweden. Icelandic Heart Association, Kopavogur, Iceland. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA. Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan. Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom. Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. Kaiser Permanente, Division of Research, Oakland, CA, USA. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere , Finland. Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland. Ealing Hospital, Southall, Middlesex UB HW, United Kingdom. Children's Hospital Oakland Research Institute, Martin Luther King Junior Way, Oakland, CA , USA. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Queensland Institute of Medical Research, Locked Bag , Royal Brisbane Hospital, Queensland , Australia. Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse -, Mannheim, Germany. Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston , Jamaica. U Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris, France. Department of Medicine, Kuopio University Hospital, Kuopio, Finland. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland. South Karelia Central Hospital, Lappeenranta, Finland. Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW RE, United Kingdom. Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland. Department of Medicine, Lausanne University Hospital, Switzerland. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain. Center for Public Health Genomics, University of Virginia, Charlottesville, VA , USA.
Abstract summary
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.Authors & Co-authors: Willer Cristen J CJ Schmidt Ellen M EM Sengupta Sebanti S Peloso Gina M GM Gustafsson Stefan S Kanoni Stavroula S Ganna Andrea A Chen Jin J Buchkovich Martin L ML Mora Samia S Beckmann Jacques S JS Bragg-Gresham Jennifer L JL Chang Hsing-Yi HY Demirkan Ayşe A Den Hertog Heleen M HM Do Ron R Donnelly Louise A LA Ehret Georg B GB Esko Tõnu T Feitosa Mary F MF Ferreira Teresa T Fischer Krista K Fontanillas Pierre P Fraser Ross M RM Freitag Daniel F DF Gurdasani Deepti D Heikkilä Kauko K Hyppönen Elina E Isaacs Aaron A Jackson Anne U AU Johansson Åsa Å Johnson Toby T Kaakinen Marika M Kettunen Johannes J Kleber Marcus E ME Li Xiaohui X Luan Jian'an J Lyytikäinen Leo-Pekka LP Magnusson Patrik K E PKE Mangino Massimo M Mihailov Evelin E Montasser May E ME Müller-Nurasyid Martina M Nolte Ilja M IM O'Connell Jeffrey R JR Palmer Cameron D CD Perola Markus M Petersen Ann-Kristin AK Sanna Serena S Saxena Richa R Service Susan K SK Shah Sonia S Shungin Dmitry D Sidore Carlo C Song Ci C Strawbridge Rona J RJ Surakka Ida I Tanaka Toshiko T Teslovich Tanya M TM Thorleifsson Gudmar G Van den Herik Evita G EG Voight Benjamin F BF Volcik Kelly A KA Waite Lindsay L LL Wong Andrew A Wu Ying Y Zhang Weihua W Absher Devin D Asiki Gershim G Barroso Inês I Been Latonya F LF Bolton Jennifer L JL Bonnycastle Lori L LL Brambilla Paolo P Burnett Mary S MS Cesana Giancarlo G Dimitriou Maria M Doney Alex S F ASF Döring Angela A Elliott Paul P Epstein Stephen E SE Ingi Eyjolfsson Gudmundur G Gigante Bruna B Goodarzi Mark O MO Grallert Harald H Gravito Martha L ML Groves Christopher J CJ Hallmans Göran G Hartikainen Anna-Liisa AL Hayward Caroline C Hernandez Dena D Hicks Andrew A AA Holm Hilma H Hung Yi-Jen YJ Illig Thomas T Jones Michelle R MR Kaleebu Pontiano P Kastelein John J P JJP Khaw Kay-Tee KT Kim Eric E Klopp Norman N Komulainen Pirjo P Kumari Meena M Langenberg Claudia C Lehtimäki Terho T Lin Shih-Yi SY Lindström Jaana J Loos Ruth J F RJF Mach François F McArdle Wendy L WL Meisinger Christa C Mitchell Braxton D BD Müller Gabrielle G Nagaraja Ramaiah R Narisu Narisu N Nieminen Tuomo V M TVM Nsubuga Rebecca N RN Olafsson Isleifur I Ong Ken K KK Palotie Aarno A Papamarkou Theodore T Pomilla Cristina C Pouta Anneli A Rader Daniel J DJ Reilly Muredach P MP Ridker Paul M PM Rivadeneira Fernando F Rudan Igor I Ruokonen Aimo A Samani Nilesh N Scharnagl Hubert H Seeley Janet J Silander Kaisa K Stančáková Alena A Stirrups Kathleen K Swift Amy J AJ Tiret Laurence L Uitterlinden Andre G AG van Pelt L Joost LJ Vedantam Sailaja S Wainwright Nicholas N Wijmenga Cisca C Wild Sarah H SH Willemsen Gonneke G Wilsgaard Tom T Wilson James F JF Young Elizabeth H EH Zhao Jing Hua JH Adair Linda S LS Arveiler Dominique D Assimes Themistocles L TL Bandinelli Stefania S Bennett Franklyn F Bochud Murielle M Boehm Bernhard O BO Boomsma Dorret I DI Borecki Ingrid B IB Bornstein Stefan R SR Bovet Pascal P Burnier Michel M Campbell Harry H Chakravarti Aravinda A Chambers John C JC Chen Yii-Der Ida YI Collins Francis S FS Cooper Richard S RS Danesh John J Dedoussis George G de Faire Ulf U Feranil Alan B AB Ferrières Jean J Ferrucci Luigi L Freimer Nelson B NB Gieger Christian C Groop Leif C LC Gudnason Vilmundur V Gyllensten Ulf U Hamsten Anders A Harris Tamara B TB Hingorani Aroon A Hirschhorn Joel N JN Hofman Albert A Hovingh G Kees GK Hsiung Chao Agnes CA Humphries Steve E SE Hunt Steven C SC Hveem Kristian K Iribarren Carlos C Järvelin Marjo-Riitta MR Jula Antti A Kähönen Mika M Kaprio Jaakko J Kesäniemi Antero A Kivimaki Mika M Kooner Jaspal S JS Koudstaal Peter J PJ Krauss Ronald M RM Kuh Diana D Kuusisto Johanna J Kyvik Kirsten O KO Laakso Markku M Lakka Timo A TA Lind Lars L Lindgren Cecilia M CM Martin Nicholas G NG März Winfried W McCarthy Mark I MI McKenzie Colin A CA Meneton Pierre P Metspalu Andres A Moilanen Leena L Morris Andrew D AD Munroe Patricia B PB Njølstad Inger I Pedersen Nancy L NL Power Chris C Pramstaller Peter P PP Price Jackie F JF Psaty Bruce M BM Quertermous Thomas T Rauramaa Rainer R Saleheen Danish D Salomaa Veikko V Sanghera Dharambir K DK Saramies Jouko J Schwarz Peter E H PEH Sheu Wayne H-H WH Shuldiner Alan R AR Siegbahn Agneta A Spector Tim D TD Stefansson Kari K Strachan David P DP Tayo Bamidele O BO Tremoli Elena E Tuomilehto Jaakko J Uusitupa Matti M van Duijn Cornelia M CM Vollenweider Peter P Wallentin Lars L Wareham Nicholas J NJ Whitfield John B JB Wolffenbuttel Bruce H R BHR Ordovas Jose M JM Boerwinkle Eric E Palmer Colin N A CNA Thorsteinsdottir Unnur U Chasman Daniel I DI Rotter Jerome I JI Franks Paul W PW Ripatti Samuli S Cupples L Adrienne LA Sandhu Manjinder S MS Rich Stephen S SS Boehnke Michael M Deloukas Panos P Kathiresan Sekar S Mohlke Karen L KL Ingelsson Erik E Abecasis Gonçalo R GR
Study Outcome
Source Link: Visit source
Statistics
Citations : 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.Authors : 260
Identifiers
Doi : 10.1038/ng.2797SSN : 1546-1718