Kuwait Medical Electronic Library

Exome-wide association study of plasma lipids in >300,000 individuals

Dajiang J Liu 1, Gina M Peloso 2 3, Haojie Yu 4, Adam S Butterworth 5 6, Xiao Wang 7, Anubha Mahajan 8, Danish Saleheen 5 9 10, Connor Emdin 3 11, Dewan Alam 12, Alexessander Couto Alves 13, Philippe Amouyel 14, Emanuele Di Angelantonio 5 6, Dominique Arveiler 15, Themistocles L Assimes 16 17, Paul L Auer 18, Usman Baber 19, Christie M Ballantyne 20, Lia E Bang 21, Marianne Benn 22 23, Joshua C Bis 24, Michael Boehnke 25, Eric Boerwinkle 26 27, Jette Bork-Jensen 28, Erwin P Bottinger 29, Ivan Brandslund 30 31, Morris Brown 32, Fabio Busonero 33, Mark J Caulfield 32 34 35, John C Chambers 36 37 38, Daniel I Chasman 39 40, Y Eugene Chen 41, Yii-Der Ida Chen 42, Rajiv Chowdhury 5, Cramer Christensen 43, Audrey Y Chu 39 44, John M Connell 45, Francesco Cucca 33 46, L Adrienne Cupples 2 44, Scott M Damrauer 47 48, Gail Davies 49 50, Ian J Deary 49 50, George Dedoussis 51, Joshua C Denny 52 53, Anna Dominiczak 54, Marie-Pierre Dubé 55 56 57, Tapani Ebeling 58, Gudny Eiriksdottir 59, Tõnu Esko 3 60, Aliki-Eleni Farmaki 51, Mary F Feitosa 61, Marco Ferrario 62, Jean Ferrieres 63, Ian Ford 64, Myriam Fornage 65, Paul W Franks 66 67 68, Timothy M Frayling 69, Ruth Frikke-Schmidt 22 23, Lars G Fritsche 25, Philippe Frossard 10, Valentin Fuster 19 70, Santhi K Ganesh 41 71, Wei Gao 72, Melissa E Garcia 73, Christian Gieger 74 75 76, Franco Giulianini 39, Mark O Goodarzi 77 78, Harald Grallert 74 75 76, Niels Grarup 28, Leif Groop 79, Megan L Grove 26, Vilmundur Gudnason 59 80, Torben Hansen 28 81, Tamara B Harris 82, Caroline Hayward 83, Joel N Hirschhorn 3 84, Oddgeir L Holmen 85 86, Jennifer Huffman 83, Yong Huo 87, Kristian Hveem 88, Sehrish Jabeen 10, Anne U Jackson 25, Johanna Jakobsdottir 59 89, Marjo-Riitta Jarvelin 13, Gorm B Jensen 90, Marit E Jørgensen 91 92, J Wouter Jukema 93 94, Johanne M Justesen 28, Pia R Kamstrup 95, Stavroula Kanoni 96, Fredrik Karpe 97 98, Frank Kee 99, Amit V Khera 3 11, Derek Klarin 3 11 100, Heikki A Koistinen 101 102 103, Jaspal S Kooner 37 38 104, Charles Kooperberg 105, Kari Kuulasmaa 101, Johanna Kuusisto 106, Markku Laakso 106, Timo Lakka 107 108 109, Claudia Langenberg 110, Anne Langsted 95 111, Lenore J Launer 82, Torsten Lauritzen 112, David C M Liewald 49 50, Li An Lin 65, Allan Linneberg 113 114 115, Ruth J F Loos 29 116, Yingchang Lu 29, Xiangfeng Lu 41 117, Reedik Mägi 60, Anders Malarstig 118 119, Ani Manichaikul 120, Alisa K Manning 3 11 121, Pekka Mäntyselkä 122, Eirini Marouli 96, Nicholas G D Masca 123 124, Andrea Maschio 33, James B Meigs 3 121 125, Olle Melander 126, Andres Metspalu 60, Andrew P Morris 8 127, Alanna C Morrison 26, Antonella Mulas 33, Martina Müller-Nurasyid 76 128 129, Patricia B Munroe 32 35, Matt J Neville 97, Jonas B Nielsen 41, Sune F Nielsen 95 111, Børge G Nordestgaard 95 111, Jose M Ordovas 130 131 132, Roxana Mehran 19, Christoper J O'Donnell 100 40, Marju Orho-Melander 126, Cliona M Molony 133, Pieter Muntendam 134, Sandosh Padmanabhan 54, Colin N A Palmer 45, Dorota Pasko 69, Aniruddh P Patel 3 11 40 135, Oluf Pedersen 28, Markus Perola 101 136, Annette Peters 74 76 129, Charlotta Pisinger 115, Giorgio Pistis 33, Ozren Polasek 137 138, Neil Poulter 139, Bruce M Psaty 24 140 141, Daniel J Rader 142, Asif Rasheed 10, Rainer Rauramaa 108 109, Dermot F Reilly 133, Alex P Reiner 105 143, Frida Renström 66 144, Stephen S Rich 120, Paul M Ridker 39, John D Rioux 55, Neil R Robertson 8 97, Dan M Roden 52 53, Jerome I Rotter 42, Igor Rudan 138, Veikko Salomaa 101, Nilesh J Samani 123 124, Serena Sanna 33, Naveed Sattar 54 97, Ellen M Schmidt 145, Robert A Scott 110, Peter Sever 139, Raquel S Sevilla 146, Christian M Shaffer 53, Xueling Sim 25 147, Suthesh Sivapalaratnam 148, Kerrin S Small 149, Albert V Smith 59 80, Blair H Smith 150 151, Sangeetha Somayajula 152, Lorraine Southam 8 153, Timothy D Spector 149, Elizabeth K Speliotes 145 154, John M Starr 49 155, Kathleen E Stirrups 96 156, Nathan Stitziel 157 158, Konstantin Strauch 159 160, Heather M Stringham 25, Praveen Surendran 5, Hayato Tada 161, Alan R Tall 162, Hua Tang 163, Jean-Claude Tardif 55 57, Kent D Taylor 42, Stella Trompet 93 164, Philip S Tsao 16 17, Jaakko Tuomilehto 165 166 167 168, Anne Tybjaerg-Hansen 22 23, Natalie R van Zuydam 8 45, Anette Varbo 95 111, Tibor V Varga 66, Jarmo Virtamo 101, Melanie Waldenberger 75 76 129, Nan Wang 162, Nick J Wareham 110, Helen R Warren 32 35, Peter E Weeke 53 169, Joshua Weinstock 25, Jennifer Wessel 170 171, James G Wilson 172, Peter W F Wilson 173 174, Ming Xu 175, Hanieh Yaghootkar 69, Robin Young 5, Eleftheria Zeggini 153, He Zhang 41, Neil S Zheng 176, Weihua Zhang 36, Yan Zhang 87, Wei Zhou 145, Yanhua Zhou 2, Magdalena Zoledziewska 33; Charge Diabetes Working Group; EPIC-InterAct Consortium; EPIC-CVD Consortium; GOLD Consortium; VA Million Veteran Program; Joanna M M Howson 5, John Danesh 5 6 153, Mark I McCarthy 8 97 98, Chad A Cowan 4 177, Goncalo Abecasis 25, Panos Deloukas 96 178, Kiran Musunuru 7, Cristen J Willer 41 71 145, Sekar Kathiresan 3 11 40 135

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Affiliations

1Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA.
2Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
3Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
4Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA.
5MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
6The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Cambridge, UK.
7Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
8Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
9Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
10Center for Non-Communicable Diseases, Karachi, Pakistan.
11Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
12ICDDR, B, Dhaka, Bangladesh.
13Imperial College London, London, UK.
14Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-related Diseases, Lille, France.
15Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France.
16VA Palo Alto Health Care System, Palo Alto, California, USA.
17Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.
18Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA.
19Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
20Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
21Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
22Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
23Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
24Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
25Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.
26Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
27Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
28The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
29The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, New York, USA.
30Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark.
31Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
32Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
33Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy.
34The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London, UK.
35NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK.
36Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
37Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK.
38Imperial College Healthcare NHS Trust, London, UK.
39Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
40Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
41Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA.
42The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Departments of Pediatrics and Medicine, Los Angeles, California, USA.
43Medical Department, Lillebaelt Hospital, Vejle, Denmark.
44NHLBI Framingham Heart Study, Framingham, Massachusetts, USA.
45Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
46Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy.
47Corporal Michael Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA.
48Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
49Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
50Department of Psychology, University of Edinburgh, Edinburgh, UK.
51Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
52Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
53Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
54British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
55Montreal Heart Institute, Montreal, Quebec, Canada.
56Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
57Université de Montréal, Montreal, Quebec, Canada.
58Department of Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland.
59The Icelandic Heart Association, Kopavogur, Iceland.
60Estonian Genome Center, University of Tartu, Tartu, Estonia.
61Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
62Research Centre in Epidemiology and Preventive Medicine-EPIMED, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
63Department of Epidemiology, UMR 1027-INSERM, Toulouse University-CHU Toulouse, Toulouse, France.
64Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
65Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
66Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
67Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden.
68Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
69Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
70Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
71Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
72Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China.
73National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
74German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
75Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
76Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
77Departments of Medicine and of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
78Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA.
79Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Centre, Lund University, Malmö, Sweden.
80Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
81Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
82Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.
83Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
84Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.
85Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway.
86St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
87Department of Cardiology, Peking University First Hospital, Beijing, China.
88K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
89Department of Health Sciences, University of Iceland, Reykjavik, Iceland.
90The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark.
91Steno Diabetes Center, Gentofte, Denmark.
92National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark.
93Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
94The Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
95Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
96William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
97Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
98Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
99UKCRC Centre of Excellence for Public Health, Queens University, Belfast, UK.
100Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA.
101Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
102Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
103Minerva Foundation Institute for Medical Research, Helsinki, Finland.
104National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK.
105Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
106Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
107Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.
108Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
109Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
110MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
111Faculty of Health and Medical Sciences, University of Denmark, Copenhagen, Denmark.
112Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark.
113Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
114Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
115Research Center for Prevention and Health, Copenhagen, Denmark.
116The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, New York, USA.
117State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
118Cardiovascular Genetics and Genomics Group, Cardiovascular Medicine Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
119Pharmatherapeutics Clinical Research, Pfizer Worldwide R&D, Sollentuna, Sweden.
120Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA.
121Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
122Unit of Primary Health Care, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
123Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
124NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
125Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
126Department of Clinical Sciences, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden.
127Department of Biostatistics, University of Liverpool, Liverpool, UK.
128Department of Medicine I, Ludwig-Maximilians-University, Munich, Germany.
129DZHK German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany.
130Department of Cardiovascular Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain.
131IMDEA-Alimentacion, Madrid, Spain.
132Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA.
133Genetics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA.
134G3 Pharmaceuticals, Lexington, Massachusetts, USA.
135Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
136Institute of Molecular Medicine FIMM, University of Helsinki, Finland.
137Faculty of Medicine, University of Split, Split, Croatia.
138Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
139International Centre for Circulatory Health, Imperial College London, London, UK.
140Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA.
141Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington, USA.
142Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
143Department of Epidemiology, University of Washington, Seattle, Washington, USA.
144Department of Biobank Research, Umeå University, Umeå, Sweden.
145Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
146Imaging, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA.
147Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
148Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
149Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
150Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
151Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
152Scientific Informatics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA.
153Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.
154Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.
155Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
156Department of Haematology, University of Cambridge, Cambridge, UK.
157Cardiovascular Division, Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
158The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA.
159IBE, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Germany.
160Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
161Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
162Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York, USA.
163Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
164Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
165Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
166Dasman Diabetes Institute, Dasman, Kuwait.
167Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.
168Saudi Diabetes Research Group, King Abdulaziz University, Fahd Medical Research Center, Jeddah, Saudi Arabia.
169The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
170Department of Epidemiology, Indiana University Fairbanks School of Public Health, Indianapolis, Indiana, USA.
171Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
172Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
173Atlanta VA Medical Center, Decatur, Georgia, USA.
174Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA.
175Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
176Yale College, Yale University, New Haven, Connecticut, USA.
177Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
178Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.

01 December 2017

doi: 10.1038/ng.3977

Abstract

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

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Exome-wide association study of plasma lipids in >300,000 individuals

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