Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Coronary Artery Disease: HELP
Articles by Yii-der Ida Chen
Based on 13 articles published since 2009
(Why 13 articles?)
||||

Between 2009 and 2019, Yii-Der Chen wrote the following 13 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Clinical Trial Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. 2017

Dewey, Frederick E / Gusarova, Viktoria / Dunbar, Richard L / O'Dushlaine, Colm / Schurmann, Claudia / Gottesman, Omri / McCarthy, Shane / Van Hout, Cristopher V / Bruse, Shannon / Dansky, Hayes M / Leader, Joseph B / Murray, Michael F / Ritchie, Marylyn D / Kirchner, H Lester / Habegger, Lukas / Lopez, Alex / Penn, John / Zhao, An / Shao, Weiping / Stahl, Neil / Murphy, Andrew J / Hamon, Sara / Bouzelmat, Aurelie / Zhang, Rick / Shumel, Brad / Pordy, Robert / Gipe, Daniel / Herman, Gary A / Sheu, Wayne H H / Lee, I-Te / Liang, Kae-Woei / Guo, Xiuqing / Rotter, Jerome I / Chen, Yii-Der I / Kraus, William E / Shah, Svati H / Damrauer, Scott / Small, Aeron / Rader, Daniel J / Wulff, Anders Berg / Nordestgaard, Børge G / Tybjærg-Hansen, Anne / van den Hoek, Anita M / Princen, Hans M G / Ledbetter, David H / Carey, David J / Overton, John D / Reid, Jeffrey G / Sasiela, William J / Banerjee, Poulabi / Shuldiner, Alan R / Borecki, Ingrid B / Teslovich, Tanya M / Yancopoulos, George D / Mellis, Scott J / Gromada, Jesper / Baras, Aris. ·From Regeneron Genetics Center (F.E.D., C.O., C.S., O.G., S.M., C.V.V.H., S.B., L.H., A.L., J.P., N.S., A.J.M., J.D.O., J.G.R., A.R.S., I.B.B., T.M.T., G.D.Y., S.J.M., A. Baras) and Regeneron Pharmaceuticals (V.G., H.M.D., A.Z., W.S., N.S., A.J.M., S.H., A. Bouzelmat, R.Z., B.S., R.P., D.G., G.A.H., W.J.S., P.B., G.D.Y., S.J.M., J.G.) Tarrytown, NY · the Department of Medicine, Division of Translational Medicine and Human Genetics (R.L.D.), and Departments of Surgery (S.D.) and Genetics and Medicine (A.S., D.J.R.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, and Geisinger Health System, Danville (J.B.L., M.F.M., M.D.R., H.L.K., D.H.L., D.J.C.) - both in Pennsylvania · the Division of Endocrinology and Metabolism, Department of Internal Medicine (W.H.H.S., I.-T.L.) and Cardiovascular Center (K.-W.L.), Taichung Veterans General Hospital, Institute of Medical Technology, National Chung-Hsing University (W.H.H.S.), School of Medicine, Chung Shan Medical University (I.-T.L.), and the Department of Medicine, China Medical University (K.-W.L.), Taichung, and School of Medicine, National Yang-Ming University (W.H.H.S., I.-T.L., K.-W.L.), and School of Medicine, National Defense Medical Center (W.H.H.S.), Taipei - all in Taiwan · Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (X.G., J.I.R., Y.-D.I.C.) · the Division of Cardiology, Department of Medicine, Molecular Physiology Institute, School of Medicine, Duke University, Durham, NC (W.E.K., S.H.S.) · the Department of Clinical Biochemistry, Rigshospitalet (A.B.W., B.G.N., A.T.-H.), the Copenhagen General Population Study (B.G.N., A.T.-H.) and Department of Clinical Biochemistry (B.G.N.), Herlev and Gentofte Hospital, and the Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, and Faculty of Health and Medical Sciences, University of Copenhagen (B.G.N., A.T.-H.) - all in Copenhagen · and TNO Metabolic Health Research, Gaubius Laboratory, Leiden, the Netherlands (A.M.H., H.M.G.P.). ·N Engl J Med · Pubmed #28538136.

ABSTRACT: BACKGROUND: Loss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. METHODS: We sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol. RESULTS: In the DiscovEHR study, participants with heterozygous loss-of-function variants in ANGPTL3 had significantly lower serum levels of triglycerides, HDL cholesterol, and LDL cholesterol than participants without these variants. Loss-of-function variants were found in 0.33% of case patients with coronary artery disease and in 0.45% of controls (adjusted odds ratio, 0.59; 95% confidence interval, 0.41 to 0.85; P=0.004). These results were confirmed in the follow-up studies. In dyslipidemic mice, inhibition of Angptl3 with evinacumab resulted in a greater decrease in atherosclerotic lesion area and necrotic content than a control antibody. In humans, evinacumab caused a dose-dependent placebo-adjusted reduction in fasting triglyceride levels of up to 76% and LDL cholesterol levels of up to 23%. CONCLUSIONS: Genetic and therapeutic antagonism of ANGPTL3 in humans and of Angptl3 in mice was associated with decreased levels of all three major lipid fractions and decreased odds of atherosclerotic cardiovascular disease. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT01749878 .).

2 Article Exome-wide association study of plasma lipids in >300,000 individuals. 2017

Liu, Dajiang J / Peloso, Gina M / Yu, Haojie / Butterworth, Adam S / Wang, Xiao / Mahajan, Anubha / Saleheen, Danish / Emdin, Connor / Alam, Dewan / Alves, Alexessander Couto / Amouyel, Philippe / Di Angelantonio, Emanuele / Arveiler, Dominique / Assimes, Themistocles L / Auer, Paul L / Baber, Usman / Ballantyne, Christie M / Bang, Lia E / Benn, Marianne / Bis, Joshua C / Boehnke, Michael / Boerwinkle, Eric / Bork-Jensen, Jette / Bottinger, Erwin P / Brandslund, Ivan / Brown, Morris / Busonero, Fabio / Caulfield, Mark J / Chambers, John C / Chasman, Daniel I / Chen, Y Eugene / Chen, Yii-Der Ida / Chowdhury, Rajiv / Christensen, Cramer / Chu, Audrey Y / Connell, John M / Cucca, Francesco / Cupples, L Adrienne / Damrauer, Scott M / Davies, Gail / Deary, Ian J / Dedoussis, George / Denny, Joshua C / Dominiczak, Anna / Dubé, Marie-Pierre / Ebeling, Tapani / Eiriksdottir, Gudny / Esko, Tõnu / Farmaki, Aliki-Eleni / Feitosa, Mary F / Ferrario, Marco / Ferrieres, Jean / Ford, Ian / Fornage, Myriam / Franks, Paul W / Frayling, Timothy M / Frikke-Schmidt, Ruth / Fritsche, Lars G / Frossard, Philippe / Fuster, Valentin / Ganesh, Santhi K / Gao, Wei / Garcia, Melissa E / Gieger, Christian / Giulianini, Franco / Goodarzi, Mark O / Grallert, Harald / Grarup, Niels / Groop, Leif / Grove, Megan L / Gudnason, Vilmundur / Hansen, Torben / Harris, Tamara B / Hayward, Caroline / Hirschhorn, Joel N / Holmen, Oddgeir L / Huffman, Jennifer / Huo, Yong / Hveem, Kristian / Jabeen, Sehrish / Jackson, Anne U / Jakobsdottir, Johanna / Jarvelin, Marjo-Riitta / Jensen, Gorm B / Jørgensen, Marit E / Jukema, J Wouter / Justesen, Johanne M / Kamstrup, Pia R / Kanoni, Stavroula / Karpe, Fredrik / Kee, Frank / Khera, Amit V / Klarin, Derek / Koistinen, Heikki A / Kooner, Jaspal S / Kooperberg, Charles / Kuulasmaa, Kari / Kuusisto, Johanna / Laakso, Markku / Lakka, Timo / Langenberg, Claudia / Langsted, Anne / Launer, Lenore J / Lauritzen, Torsten / Liewald, David C M / Lin, Li An / Linneberg, Allan / Loos, Ruth J F / Lu, Yingchang / Lu, Xiangfeng / Mägi, Reedik / Malarstig, Anders / Manichaikul, Ani / Manning, Alisa K / Mäntyselkä, Pekka / Marouli, Eirini / Masca, Nicholas G D / Maschio, Andrea / Meigs, James B / Melander, Olle / Metspalu, Andres / Morris, Andrew P / Morrison, Alanna C / Mulas, Antonella / Müller-Nurasyid, Martina / Munroe, Patricia B / Neville, Matt J / Nielsen, Jonas B / Nielsen, Sune F / Nordestgaard, Børge G / Ordovas, Jose M / Mehran, Roxana / O'Donnell, Christoper J / Orho-Melander, Marju / Molony, Cliona M / Muntendam, Pieter / Padmanabhan, Sandosh / Palmer, Colin N A / Pasko, Dorota / Patel, Aniruddh P / Pedersen, Oluf / Perola, Markus / Peters, Annette / Pisinger, Charlotta / Pistis, Giorgio / Polasek, Ozren / Poulter, Neil / Psaty, Bruce M / Rader, Daniel J / Rasheed, Asif / Rauramaa, Rainer / Reilly, Dermot F / Reiner, Alex P / Renström, Frida / Rich, Stephen S / Ridker, Paul M / Rioux, John D / Robertson, Neil R / Roden, Dan M / Rotter, Jerome I / Rudan, Igor / Salomaa, Veikko / Samani, Nilesh J / Sanna, Serena / Sattar, Naveed / Schmidt, Ellen M / Scott, Robert A / Sever, Peter / Sevilla, Raquel S / Shaffer, Christian M / Sim, Xueling / Sivapalaratnam, Suthesh / Small, Kerrin S / Smith, Albert V / Smith, Blair H / Somayajula, Sangeetha / Southam, Lorraine / Spector, Timothy D / Speliotes, Elizabeth K / Starr, John M / Stirrups, Kathleen E / Stitziel, Nathan / Strauch, Konstantin / Stringham, Heather M / Surendran, Praveen / Tada, Hayato / Tall, Alan R / Tang, Hua / Tardif, Jean-Claude / Taylor, Kent D / Trompet, Stella / Tsao, Philip S / Tuomilehto, Jaakko / Tybjaerg-Hansen, Anne / van Zuydam, Natalie R / Varbo, Anette / Varga, Tibor V / Virtamo, Jarmo / Waldenberger, Melanie / Wang, Nan / Wareham, Nick J / Warren, Helen R / Weeke, Peter E / Weinstock, Joshua / Wessel, Jennifer / Wilson, James G / Wilson, Peter W F / Xu, Ming / Yaghootkar, Hanieh / Young, Robin / Zeggini, Eleftheria / Zhang, He / Zheng, Neil S / Zhang, Weihua / Zhang, Yan / Zhou, Wei / Zhou, Yanhua / Zoledziewska, Magdalena / Anonymous821322 / Anonymous831322 / Anonymous841322 / Anonymous851322 / Anonymous861322 / Howson, Joanna M M / Danesh, John / McCarthy, Mark I / Cowan, Chad A / Abecasis, Goncalo / Deloukas, Panos / Musunuru, Kiran / Willer, Cristen J / Kathiresan, Sekar. ·Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. · Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA. · MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. · The National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Cambridge, UK. · Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Center for Non-Communicable Diseases, Karachi, Pakistan. · Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · ICDDR, B, Dhaka, Bangladesh. · Imperial College London, London, UK. · Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Determinants of Aging-related Diseases, Lille, France. · Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France. · VA Palo Alto Health Care System, Palo Alto, California, USA. · Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. · Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA. · Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. · Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. · Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. · Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA. · Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. · Human 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. · Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. · The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · The Charles Bronfman Institute for Personalized Medicine, Ichan School of Medicine at Mount Sinai, New York, New York, USA. · Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark. · Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark. · Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy. · The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London, UK. · NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, UK. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Department of Cardiology, Ealing Hospital NHS Trust, Southall, UK. · Imperial College Healthcare NHS Trust, London, UK. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. · Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA. · The Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Departments of Pediatrics and Medicine, Los Angeles, California, USA. · Medical Department, Lillebaelt Hospital, Vejle, Denmark. · NHLBI Framingham Heart Study, Framingham, Massachusetts, USA. · Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy. · Corporal Michael Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA. · Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · Department of Psychology, University of Edinburgh, Edinburgh, UK. · Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece. · Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. · Montreal Heart Institute, Montreal, Quebec, Canada. · Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada. · Université de Montréal, Montreal, Quebec, Canada. · Department of Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland. · The Icelandic Heart Association, Kopavogur, Iceland. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA. · Research Centre in Epidemiology and Preventive Medicine-EPIMED, Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Department of Epidemiology, UMR 1027-INSERM, Toulouse University-CHU Toulouse, Toulouse, France. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. · Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA. · Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden. · Department of Public Health & Clinical Medicine, Umeå University, Umeå, Sweden. · Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. · Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK. · Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. · Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. · Department of Cardiology, Peking University Third Hospital, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China. · National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA. · German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany. · Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany. · Departments of Medicine and of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Department of Clinical Sciences, Diabetes and Endocrinology, Clinical Research Centre, Lund University, Malmö, Sweden. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. · Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA. · Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA. · Department of Public Health and General Practice, HUNT Research Centre, Norwegian University of Science and Technology, Levanger, Norway. · St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. · Department of Cardiology, Peking University First Hospital, Beijing, China. · K. 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. · Department of Health Sciences, University of Iceland, Reykjavik, Iceland. · The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark. · Steno Diabetes Center, Gentofte, Denmark. · National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark. · Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands. · The Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands. · Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. · Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK. · UKCRC Centre of Excellence for Public Health, Queens University, Belfast, UK. · Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, Massachusetts, USA. · Department of Health, National Institute for Health and Welfare, Helsinki, Finland. · Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. · Minerva Foundation Institute for Medical Research, Helsinki, Finland. · National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, London, UK. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. · Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland. · Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. · Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Faculty of Health and Medical Sciences, University of Denmark, Copenhagen, Denmark. · Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark. · Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. · Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Research Center for Prevention and Health, Copenhagen, Denmark. · The Mindich Child Health and Development Institute, Ichan School of Medicine at Mount Sinai, New York, New York, USA. · State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Cardiovascular Genetics and Genomics Group, Cardiovascular Medicine Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. · Pharmatherapeutics Clinical Research, Pfizer Worldwide R&D, Sollentuna, Sweden. · Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia, USA. · Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Unit of Primary Health Care, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. · Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. · NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. · Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Clinical Sciences, University Hospital Malmo Clinical Research Center, Lund University, Malmo, Sweden. · Department of Biostatistics, University of Liverpool, Liverpool, UK. · Department of Medicine I, Ludwig-Maximilians-University, Munich, Germany. · DZHK German Centre for Cardiovascular Research, Munich Heart Alliance, Munich, Germany. · Department of Cardiovascular Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain. · IMDEA-Alimentacion, Madrid, Spain. · Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USA. · Genetics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA. · G3 Pharmaceuticals, Lexington, Massachusetts, USA. · Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. · Institute of Molecular Medicine FIMM, University of Helsinki, Finland. · Faculty of Medicine, University of Split, Split, Croatia. · Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK. · International Centre for Circulatory Health, Imperial College London, London, UK. · Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA. · Departments of Epidemiology and Health Services, University of Washington, Seattle, Washington, USA. · Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Biobank Research, Umeå University, Umeå, Sweden. · Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. · Imaging, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA. · Saw Swee Hock School of Public Health, National University of Singapore, Singapore. · Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. · Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK. · Scientific Informatics, Merck Sharp & Dohme Corporation, Kenilworth, New Jersey, USA. · Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK. · Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA. · Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK. · Department of Haematology, University of Cambridge, Cambridge, UK. · Cardiovascular Division, Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, Missouri, USA. · The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA. · IBE, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Germany. · Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. · Division of Cardiovascular Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. · Department of Medicine, Division of Molecular Medicine, Columbia University, New York, New York, USA. · Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. · Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands. · Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland. · Dasman Diabetes Institute, Dasman, Kuwait. · Centre for Vascular Prevention, Danube-University Krems, Krems, Austria. · Saudi Diabetes Research Group, King Abdulaziz University, Fahd Medical Research Center, Jeddah, Saudi Arabia. · The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. · Department of Epidemiology, Indiana University Fairbanks School of Public Health, Indianapolis, Indiana, USA. · Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA. · Atlanta VA Medical Center, Decatur, Georgia, USA. · Emory Clinical Cardiovascular Research Institute, Atlanta, Georgia, USA. · Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China. · Yale College, Yale University, New Haven, Connecticut, USA. · Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia. ·Nat Genet · Pubmed #29083408.

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.

3 Article Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease. 2017

Lu, Xiangfeng / Peloso, Gina M / Liu, Dajiang J / Wu, Ying / Zhang, He / Zhou, Wei / Li, Jun / Tang, Clara Sze-Man / Dorajoo, Rajkumar / Li, Huaixing / Long, Jirong / Guo, Xiuqing / Xu, Ming / Spracklen, Cassandra N / Chen, Yang / Liu, Xuezhen / Zhang, Yan / Khor, Chiea Chuen / Liu, Jianjun / Sun, Liang / Wang, Laiyuan / Gao, Yu-Tang / Hu, Yao / Yu, Kuai / Wang, Yiqin / Cheung, Chloe Yu Yan / Wang, Feijie / Huang, Jianfeng / Fan, Qiao / Cai, Qiuyin / Chen, Shufeng / Shi, Jinxiu / Yang, Xueli / Zhao, Wanting / Sheu, Wayne H-H / Cherny, Stacey Shawn / He, Meian / Feranil, Alan B / Adair, Linda S / Gordon-Larsen, Penny / Du, Shufa / Varma, Rohit / Chen, Yii-Der Ida / Shu, Xiao-Ou / Lam, Karen Siu Ling / Wong, Tien Yin / Ganesh, Santhi K / Mo, Zengnan / Hveem, Kristian / Fritsche, Lars G / Nielsen, Jonas Bille / Tse, Hung-Fat / Huo, Yong / Cheng, Ching-Yu / Chen, Y Eugene / Zheng, Wei / Tai, E Shyong / Gao, Wei / Lin, Xu / Huang, Wei / Abecasis, Goncalo / Anonymous2270925 / Kathiresan, Sekar / Mohlke, Karen L / Wu, Tangchun / Sham, Pak Chung / Gu, Dongfeng / Willer, Cristen J. ·Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. · Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. · Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA. · Department of Public Health Sciences, Institute of Personalized Medicine, Penn State University, University Park, Pennsylvania, USA. · Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. · Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. · MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China. · Department of Surgery, Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Dr. Li Dak-Sum Research Centre, The University of Hong Kong-Karolinska Institutet Collaboration in Regenerative Medicine, Hong Kong, China. · Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore. · Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and University of the Chinese Academy of Sciences, Shanghai, China. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. · Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Los Angeles, California, USA. · Department of Cardiology, Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China. · Center for Genomic and Personalized Medicine, Medical Scientific Research Center and Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China. · Department of Cardiology, Peking University First Hospital, Beijing, China. · Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. · Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Medicine, the University of Hong Kong, Hong Kong, China. · Community Health Center, The 3rd Affiliated Hospital of Shenzhen University, Shenzhen, China. · Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. · Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China. · Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. · Department of Psychiatry, the University of Hong Kong, Hong Kong, China. · Centre for Genomic Sciences, Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. · State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China. · USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines. · Department of Anthropology, Sociology, and History, University of San Carlos, Cebu City, Philippines. · Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. · Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina, USA. · USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA. · Research Centre of Heart, Brain, Hormone and Healthy Aging, Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. · State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China. · Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore. · Department of Ophthalmology, National University of Singapore, Singapore, Singapore. · HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. · K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. · Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway. · Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA. · Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong, Hong Kong, China. · Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore. · Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore. · Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. ·Nat Genet · Pubmed #29083407.

ABSTRACT: Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.

4 Article Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. 2017

Howson, Joanna M M / Zhao, Wei / Barnes, Daniel R / Ho, Weang-Kee / Young, Robin / Paul, Dirk S / Waite, Lindsay L / Freitag, Daniel F / Fauman, Eric B / Salfati, Elias L / Sun, Benjamin B / Eicher, John D / Johnson, Andrew D / Sheu, Wayne H H / Nielsen, Sune F / Lin, Wei-Yu / Surendran, Praveen / Malarstig, Anders / Wilk, Jemma B / Tybjærg-Hansen, Anne / Rasmussen, Katrine L / Kamstrup, Pia R / Deloukas, Panos / Erdmann, Jeanette / Kathiresan, Sekar / Samani, Nilesh J / Schunkert, Heribert / Watkins, Hugh / Anonymous2140907 / Do, Ron / Rader, Daniel J / Johnson, Julie A / Hazen, Stanley L / Quyyumi, Arshed A / Spertus, John A / Pepine, Carl J / Franceschini, Nora / Justice, Anne / Reiner, Alex P / Buyske, Steven / Hindorff, Lucia A / Carty, Cara L / North, Kari E / Kooperberg, Charles / Boerwinkle, Eric / Young, Kristin / Graff, Mariaelisa / Peters, Ulrike / Absher, Devin / Hsiung, Chao A / Lee, Wen-Jane / Taylor, Kent D / Chen, Ying-Hsiang / Lee, I-Te / Guo, Xiuqing / Chung, Ren-Hua / Hung, Yi-Jen / Rotter, Jerome I / Juang, Jyh-Ming J / Quertermous, Thomas / Wang, Tzung-Dau / Rasheed, Asif / Frossard, Philippe / Alam, Dewan S / Majumder, Abdulla Al Shafi / Di Angelantonio, Emanuele / Chowdhury, Rajiv / Anonymous2150907 / Chen, Yii-Der Ida / Nordestgaard, Børge G / Assimes, Themistocles L / Danesh, John / Butterworth, Adam S / Saleheen, Danish. ·MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. · Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · Department of Applied Mathematics, University of Nottingham Malaysia Campus, Semenyih, Malaysia. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK. · HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA. · Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA. · Department of Medicine, Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA. · Stanford Cardiovascular Institute, Stanford University, Stanford, California, USA. · National Heart, Lung, and Blood Institute, Population Sciences Branch, Bethesda, Maryland, USA. · NHLBI and Boston University's The Framingham Heart Study, Framingham, Massachusetts, USA. · Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. · School of Medicine, National Yang-Ming University, Taipei, Taiwan. · College of Medicine, National Defense Medical Center, Taipei, Taiwan. · Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark. · Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK. · Pfizer Worldwide Research and Development, Stockholm, Sweden. · Pfizer Worldwide Research and Development, Human Genetics, Cambridge, Massachusetts, USA. · Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. · Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · Centre for Genomic Health, Queen Mary University of London, London, UK. · Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany. · DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany. · University Heart Center Lübeck, Lübeck, Germany. · Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. · Department of Cardiovascular Sciences, University of Leicester, Leicester, UK. · NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. · Deutsches Herzzentrum München, Technische Universität München, Munich, Germany. · DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. · Radcliffe Department of Medicine, University of Oxford, Oxford, UK. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Charles Bronfman Institute for Personalized Medicine, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA. · Departments of Genetics, Medicine, and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. · University of Florida College of Pharmacy, Gainesville, Florida, USA. · Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland, Ohio, USA. · Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA. · Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA. · Department of Biomedical and Health Informatics, University of Missouri-Kansas City, Kansas City, Missouri, USA. · College of Medicine, University of Florida, Gainesville, Florida, USA. · Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey, USA. · Division of Genomic Medicine, National Human Genome Research Institute, US National Institutes of Health, Bethesda,Maryland, USA. · Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Carolina Center for Genome Sciences, Chapel Hill, North Carolina, USA. · Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, USA. · Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. · Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan. · Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. · Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA. · School of Medicine, Chung Shan Medical University, Taichung, Taiwan. · Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. · Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, California, USA. · Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. · National Taiwan University College of Medicine, Taipei, Taiwan. · Centre for Non-Communicable Disease, Karachi, Pakistan. · School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada. · National Institute of Cardiovascular Diseases, Sher-e-Bangla Nagar, Bangladesh. · National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK. · Wellcome Trust Sanger Institute, Hinxton, UK. · British Heart Foundation Cambridge Centre of Excellence, Department of Medicine, University of Cambridge, Cambridge, UK. ·Nat Genet · Pubmed #28530674.

ABSTRACT: Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10

5 Article Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis. 2016

Natarajan, Pradeep / Bis, Joshua C / Bielak, Lawrence F / Cox, Amanda J / Dörr, Marcus / Feitosa, Mary F / Franceschini, Nora / Guo, Xiuqing / Hwang, Shih-Jen / Isaacs, Aaron / Jhun, Min A / Kavousi, Maryam / Li-Gao, Ruifang / Lyytikäinen, Leo-Pekka / Marioni, Riccardo E / Schminke, Ulf / Stitziel, Nathan O / Tada, Hayato / van Setten, Jessica / Smith, Albert V / Vojinovic, Dina / Yanek, Lisa R / Yao, Jie / Yerges-Armstrong, Laura M / Amin, Najaf / Baber, Usman / Borecki, Ingrid B / Carr, J Jeffrey / Chen, Yii-Der Ida / Cupples, L Adrienne / de Jong, Pim A / de Koning, Harry / de Vos, Bob D / Demirkan, Ayse / Fuster, Valentin / Franco, Oscar H / Goodarzi, Mark O / Harris, Tamara B / Heckbert, Susan R / Heiss, Gerardo / Hoffmann, Udo / Hofman, Albert / Išgum, Ivana / Jukema, J Wouter / Kähönen, Mika / Kardia, Sharon L R / Kral, Brian G / Launer, Lenore J / Massaro, Joe / Mehran, Roxana / Mitchell, Braxton D / Mosley, Thomas H / de Mutsert, Renée / Newman, Anne B / Nguyen, Khanh-Dung / North, Kari E / O'Connell, Jeffrey R / Oudkerk, Matthijs / Pankow, James S / Peloso, Gina M / Post, Wendy / Province, Michael A / Raffield, Laura M / Raitakari, Olli T / Reilly, Dermot F / Rivadeneira, Fernando / Rosendaal, Frits / Sartori, Samantha / Taylor, Kent D / Teumer, Alexander / Trompet, Stella / Turner, Stephen T / Uitterlinden, Andre G / Vaidya, Dhananjay / van der Lugt, Aad / Völker, Uwe / Wardlaw, Joanna M / Wassel, Christina L / Weiss, Stefan / Wojczynski, Mary K / Becker, Diane M / Becker, Lewis C / Boerwinkle, Eric / Bowden, Donald W / Deary, Ian J / Dehghan, Abbas / Felix, Stephan B / Gudnason, Vilmundur / Lehtimäki, Terho / Mathias, Rasika / Mook-Kanamori, Dennis O / Psaty, Bruce M / Rader, Daniel J / Rotter, Jerome I / Wilson, James G / van Duijn, Cornelia M / Völzke, Henry / Kathiresan, Sekar / Peyser, Patricia A / O'Donnell, Christopher J / Anonymous3111076. · ·Circ Cardiovasc Genet · Pubmed #27872105.

ABSTRACT: BACKGROUND: The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease. METHODS AND RESULTS: We studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10 CONCLUSIONS: Exome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.

6 Article Lymphocyte activation gene 3 and coronary artery disease. 2016

Golden, Diana / Kolmakova, Antonina / Sura, Sunitha / Vella, Anthony T / Manichaikul, Ani / Wang, Xin-Qun / Bielinski, Suzette J / Taylor, Kent D / Chen, Yii-Der Ida / Rich, Stephen S / Rodriguez, Annabelle. ·Center for Vascular Biology and. · Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut, USA. · Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia. · Biostatistics Section, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA. · Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA. · Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California, USA. ·JCI Insight · Pubmed #27777974.

ABSTRACT:

7 Article Genetics of Coronary Artery Disease in Taiwan: A Cardiometabochip Study by the Taichi Consortium. 2016

Assimes, Themistocles L / Lee, I-T / Juang, Jyh-Ming / Guo, Xiuqing / Wang, Tzung-Dau / Kim, Eric T / Lee, Wen-Jane / Absher, Devin / Chiu, Yen-Feng / Hsu, Chih-Cheng / Chuang, Lee-Ming / Quertermous, Thomas / Hsiung, Chao A / Rotter, Jerome I / Sheu, Wayne H-H / Chen, Yii-Der Ida / Taylor, Kent D. ·Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America. · Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. · Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National University College of Medicine, Taipei, Taiwan. · Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, and Department of Pediatrics, University of California Los Angeles, Los Angeles, California, United States of America. · Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. · HudsonAlpha Institute for Biotechnology, Huntsville, Alabama. · Institute of Population Health Sciences, Division of Biostatistics and Bioinformatics, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. · Division of Endocrine and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. ·PLoS One · Pubmed #26982883.

ABSTRACT: By means of a combination of genome-wide and follow-up studies, recent large-scale association studies of populations of European descent have now identified over 46 loci associated with coronary artery disease (CAD). As part of the TAICHI Consortium, we have collected and genotyped 8556 subjects from Taiwan, comprising 5423 controls and 3133 cases with coronary artery disease, for 9087 CAD SNPs using the CardioMetaboChip. We applied penalized logistic regression to ascertain the top SNPs that contribute together to CAD susceptibility in Taiwan. We observed that the 9p21 locus contributes to CAD at the level of genome-wide significance (rs1537372, with the presence of C, the major allele, the effect estimate is -0.216, standard error 0.033, p value 5.8x10-10). In contrast to a previous report, we propose that the 9p21 locus is a single genetic contribution to CAD in Taiwan because: 1) the penalized logistic regression and the follow-up conditional analysis suggested that rs1537372 accounts for all of the CAD association in 9p21, and 2) the high linkage disequilibrium observed for all associated SNPs in 9p21. We also observed evidence for the following loci at a false discovery rate >5%: SH2B3, ADAMTS7, PHACTR1, GGCX, HTRA1, COL4A1, and LARP6-LRRC49. We also took advantage of the fact that penalized methods are an efficient approach to search for gene-by-gene interactions, and observed that two-way interactions between the PHACTR1 and ADAMTS7 loci and between the SH2B3 and COL4A1 loci contribute to CAD risk. Both the similarities and differences between the significance of these loci when compared with significance of loci in studies of populations of European descent underscore the fact that further genetic association of studies in additional populations will provide clues to identify the genetic architecture of CAD across all populations worldwide.

8 Article Genetic loci associated with nonobstructive coronary artery disease in Caucasian women. 2016

Weng, Liming / Taylor, Kent D / Chen, Yii-Der Ida / Sopko, George / Kelsey, Sheryl F / Bairey Merz, C Noel / Pepine, Carl J / Miller, Virginia M / Rotter, Jerome I / Gulati, Martha / Goodarzi, Mark O / Cooper-DeHoff, Rhonda M. ·Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, Florida; · Institute for Translational Genomics and Population Sciences and Department of Pediatrics and Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Torrance, California; · National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland; · Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania; · Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California; · Division of Cardiology, College of Medicine, University of Florida, Gainesville, Florida; · Departments of Surgery and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; · Department of Medicine (Cardiology), The Ohio State University, Columbus, Ohio; and. · Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California. · Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, College of Pharmacy, Gainesville, Florida; Division of Cardiology, College of Medicine, University of Florida, Gainesville, Florida; dehoff@cop.ufl.edu. ·Physiol Genomics · Pubmed #26534935.

ABSTRACT: Nonobstructive coronary artery disease (CAD) in women is associated with adverse cardiovascular (CV) outcomes; however, information regarding genetic variants that predispose women to nonobstructive CAD is lacking. Women from the Women's Ischemia Syndrome Evaluation (WISE) Study and the St. James Women Take Heart (WTH) Study were genotyped with the Cardio-MetaboChip. WISE enrolled women with symptoms and signs of ischemia referred for coronary angiography; WTH enrolled asymptomatic, community-based women without heart disease. Analyses were conducted with a case (WISE)--control (WTH) design and multivariate logistic regression models to investigate genetic variation associated with likelihood of nonobstructive CAD. One genetic marker, single nucleotide polymorphism (SNP) rs2301753 on chromosome 6 in RNF39, achieved chip-wide significance for nonobstructive CAD (P < 9.5 × 10(-7)). After adjusting for baseline characteristics, we found no variants achieved chip-wide significance. However, SNP rs2301753 on chromosome 6 in RNF39 was associated with reduced likelihood of nonobstructive CAD [odds ratio (OR) 0.42 and 95% confidence interval (CI) of 0.29 to 0.68], at a nominal level of P = 5.6 × 10(-6), while SNP rs12818945 in the ATP2B1 locus on chromosome 12 was associated with increased odds for nonobstructive CAD (OR 2.38 and 95% CI of 1.63 to 3.45) and nominal P = 5.8 × 10(-6). The functions of RNF39 and ATP2B1 raise the possibility that genes involved in cardio-dysfunction may contribute to nonobstructive CAD in Caucasian women and may provide insights into novel approaches for therapy and prevention. If replicated, incorporation of these genetic variants into diagnostic evaluation may identify women at high risk for nonobstructive CAD.

9 Article The chromosome 9p21 variant not predicting long-term cardiovascular mortality in Chinese with established coronary artery disease: an eleven-year follow-up study. 2014

Lee, I-Te / Goodarzi, Mark O / Lee, Wen-Jane / Rotter, Jerome I / Chen, Yii-der Ida / Liang, Kae-Woei / Lee, Wen-Lieng / Sheu, Wayne H-H. ·Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan ; School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan ; School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan. · Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA ; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan. · Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA ; Department of Ob/Gyn, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Cardiovascular Center, Taichung Veterans General Hospital, Taichung 40705, Taiwan. ·Biomed Res Int · Pubmed #24804228.

ABSTRACT: INTRODUCTION: We examined whether the variant at chromosome 9p21, rs4977574, was associated with long-term cardiovascular mortality in Han Chinese patients with coronary artery disease (CAD). METHODOLOGY: Subjects who underwent coronary angiography for chest pain were consecutively enrolled. Fasting blood samples were collected for laboratory and genotype assessments. The information was correlated with data collected from the national death database. RESULTS: There were 925 cases with CAD and 634 without CAD enrolled in the present study. The G allele conferred a significant increase in risk of CAD (odds ratio = 1.47, P = 0.003 in the dominant model; odds ratio = 1.36, P = 0.018 in the recessive model). During a median of 11 years (inter-quartile range between 5.2 and 12.5 years) of follow-up, neither the total nor the cardiovascular mortality was different among CAD subjects with different genotypes. Using Cox regression analysis, genotypes of rs4977574 still failed to predict cardiovascular mortality (hazard ratio = 1.25, P = 0.138 in the dominant model; hazard ratio = 1.05, P = 0.729 in the recessive model). CONCLUSIONS: The rs4977574 at chromosome 9p21 is associated with presence of CAD in Han Chinese. However, rs4977574 could not predict cardiovascular mortality in these CAD subjects during the eleven-year period of the study.

10 Article Discovery and refinement of loci associated with lipid levels. 2013

Willer, Cristen J / Schmidt, Ellen M / Sengupta, Sebanti / Peloso, Gina M / Gustafsson, Stefan / Kanoni, Stavroula / Ganna, Andrea / Chen, Jin / Buchkovich, Martin L / Mora, Samia / Beckmann, Jacques S / Bragg-Gresham, Jennifer L / Chang, Hsing-Yi / Demirkan, Ayşe / Den Hertog, Heleen M / Do, Ron / Donnelly, Louise A / Ehret, Georg B / Esko, Tõnu / Feitosa, Mary F / Ferreira, Teresa / Fischer, Krista / Fontanillas, Pierre / Fraser, Ross M / Freitag, Daniel F / Gurdasani, Deepti / Heikkilä, Kauko / Hyppönen, Elina / Isaacs, Aaron / Jackson, Anne U / Johansson, Åsa / Johnson, Toby / Kaakinen, Marika / Kettunen, Johannes / Kleber, Marcus E / Li, Xiaohui / Luan, Jian'an / Lyytikäinen, Leo-Pekka / Magnusson, Patrik K E / Mangino, Massimo / Mihailov, Evelin / Montasser, May E / Müller-Nurasyid, Martina / Nolte, Ilja M / O'Connell, Jeffrey R / Palmer, Cameron D / Perola, Markus / Petersen, Ann-Kristin / Sanna, Serena / Saxena, Richa / Service, Susan K / Shah, Sonia / Shungin, Dmitry / Sidore, Carlo / Song, Ci / Strawbridge, Rona J / Surakka, Ida / Tanaka, Toshiko / Teslovich, Tanya M / Thorleifsson, Gudmar / Van den Herik, Evita G / Voight, Benjamin F / Volcik, Kelly A / Waite, Lindsay L / Wong, Andrew / Wu, Ying / Zhang, Weihua / Absher, Devin / Asiki, Gershim / Barroso, Inês / Been, Latonya F / Bolton, Jennifer L / Bonnycastle, Lori L / Brambilla, Paolo / Burnett, Mary S / Cesana, Giancarlo / Dimitriou, Maria / Doney, Alex S F / Döring, Angela / Elliott, Paul / Epstein, Stephen E / Ingi Eyjolfsson, Gudmundur / Gigante, Bruna / Goodarzi, Mark O / Grallert, Harald / Gravito, Martha L / Groves, Christopher J / Hallmans, Göran / Hartikainen, Anna-Liisa / Hayward, Caroline / Hernandez, Dena / Hicks, Andrew A / Holm, Hilma / Hung, Yi-Jen / Illig, Thomas / Jones, Michelle R / Kaleebu, Pontiano / Kastelein, John J P / Khaw, Kay-Tee / Kim, Eric / Klopp, Norman / Komulainen, Pirjo / Kumari, Meena / Langenberg, Claudia / Lehtimäki, Terho / Lin, Shih-Yi / Lindström, Jaana / Loos, Ruth J F / Mach, François / McArdle, Wendy L / Meisinger, Christa / Mitchell, Braxton D / Müller, Gabrielle / Nagaraja, Ramaiah / Narisu, Narisu / Nieminen, Tuomo V M / Nsubuga, Rebecca N / Olafsson, Isleifur / Ong, Ken K / Palotie, Aarno / Papamarkou, Theodore / Pomilla, Cristina / Pouta, Anneli / Rader, Daniel J / Reilly, Muredach P / Ridker, Paul M / Rivadeneira, Fernando / Rudan, Igor / Ruokonen, Aimo / Samani, Nilesh / Scharnagl, Hubert / Seeley, Janet / Silander, Kaisa / Stančáková, Alena / Stirrups, Kathleen / Swift, Amy J / Tiret, Laurence / Uitterlinden, Andre G / van Pelt, L Joost / Vedantam, Sailaja / Wainwright, Nicholas / Wijmenga, Cisca / Wild, Sarah H / Willemsen, Gonneke / Wilsgaard, Tom / Wilson, James F / Young, Elizabeth H / Zhao, Jing Hua / Adair, Linda S / Arveiler, Dominique / Assimes, Themistocles L / Bandinelli, Stefania / Bennett, Franklyn / Bochud, Murielle / Boehm, Bernhard O / Boomsma, Dorret I / Borecki, Ingrid B / Bornstein, Stefan R / Bovet, Pascal / Burnier, Michel / Campbell, Harry / Chakravarti, Aravinda / Chambers, John C / Chen, Yii-Der Ida / Collins, Francis S / Cooper, Richard S / Danesh, John / Dedoussis, George / de Faire, Ulf / Feranil, Alan B / Ferrières, Jean / Ferrucci, Luigi / Freimer, Nelson B / Gieger, Christian / Groop, Leif C / Gudnason, Vilmundur / Gyllensten, Ulf / Hamsten, Anders / Harris, Tamara B / Hingorani, Aroon / Hirschhorn, Joel N / Hofman, Albert / Hovingh, G Kees / Hsiung, Chao Agnes / Humphries, Steve E / Hunt, Steven C / Hveem, Kristian / Iribarren, Carlos / Järvelin, Marjo-Riitta / Jula, Antti / Kähönen, Mika / Kaprio, Jaakko / Kesäniemi, Antero / Kivimaki, Mika / Kooner, Jaspal S / Koudstaal, Peter J / Krauss, Ronald M / Kuh, Diana / Kuusisto, Johanna / Kyvik, Kirsten O / Laakso, Markku / Lakka, Timo A / Lind, Lars / Lindgren, Cecilia M / Martin, Nicholas G / März, Winfried / McCarthy, Mark I / McKenzie, Colin A / Meneton, Pierre / Metspalu, Andres / Moilanen, Leena / Morris, Andrew D / Munroe, Patricia B / Njølstad, Inger / Pedersen, Nancy L / Power, Chris / Pramstaller, Peter P / Price, Jackie F / Psaty, Bruce M / Quertermous, Thomas / Rauramaa, Rainer / Saleheen, Danish / Salomaa, Veikko / Sanghera, Dharambir K / Saramies, Jouko / Schwarz, Peter E H / Sheu, Wayne H-H / Shuldiner, Alan R / Siegbahn, Agneta / Spector, Tim D / Stefansson, Kari / Strachan, David P / Tayo, Bamidele O / Tremoli, Elena / Tuomilehto, Jaakko / Uusitupa, Matti / van Duijn, Cornelia M / Vollenweider, Peter / Wallentin, Lars / Wareham, Nicholas J / Whitfield, John B / Wolffenbuttel, Bruce H R / Ordovas, Jose M / Boerwinkle, Eric / Palmer, Colin N A / Thorsteinsdottir, Unnur / Chasman, Daniel I / Rotter, Jerome I / Franks, Paul W / Ripatti, Samuli / Cupples, L Adrienne / Sandhu, Manjinder S / Rich, Stephen S / Boehnke, Michael / Deloukas, Panos / Kathiresan, Sekar / Mohlke, Karen L / Ingelsson, Erik / Abecasis, Gonçalo R / Anonymous3140771. ·Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA. · Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden. · Science for Life Laboratory, Uppsala University, Uppsala, Sweden. · Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA. · Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA. · Harvard Medical School, Boston MA 02115, USA. · Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland. · Department of Medical Genetics, University of Lausanne, 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. · Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom. · Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland. · Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Estonian Genome Center of the University of Tartu, Tartu, Estonia. · Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · Department of Genetics, Washington University School of Medicine, USA. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom. · Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, 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. · Centre for Medical Systems Biology, Leiden, the Netherlands. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. · Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. · 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. · Biocenter Oulu, University of Oulu, Oulu, Finland. · Institute of Health Sciences, University of Oulu, Finland. · Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland. · Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland. · Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany. · Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany. · Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom. · Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland. · Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland. · 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 85764, Germany. · Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany. · Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany. · Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands. · Division of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA. · Division of Genetics, Program in Genomics, Children's Hospital, Boston, Massachusetts 02115, USA. · Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, 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 WC1E 6BT, United Kingdom. · Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden. · Department of Odontology, Umeå University, Umeå, Sweden. · Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden. · Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy. · Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. · Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. · Clinical Research Branch, National Institute Health, Baltimore, MD, USA. · deCODE Genetics/Amgen, 101 Reykjavik, Iceland. · Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA. · Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA. · Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA. · HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA. · MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom. · MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda. · 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. · Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA. · Department of Experimental Medicine, University of Milano Bicocca, Italy. · MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA. · Research Centre on Public Health, University of Milano Bicocca, Italy. · Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece. · Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK. · The Laboratory in Mjodd, 108 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 90048, USA. · Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany. · Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, 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 20892, 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. · Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany. · 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, 00271 Helsinki, Finland. · The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA. · The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at ount Sinai, New York, USA. · The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York. · School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom. · Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. · Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA. · Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew 33014, Finland. · Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland. · Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland. · Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland. · Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. · Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United ingdom. · Department of Statistical Sciences, University College of London, London, United Kingdom. · National Institute for Health and Welfare, Oulu, Finland. · 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. · 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. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. · Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. · Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, 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 LE3 9QP, UK. · Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK. · Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. · School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom. · University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland. · INSERM UMRS 937, 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 Genetics, 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 3430, 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 7, Jamaica. · Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland. · Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany. · Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. · Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany. · Ministry of Health, Victoria, Republic of Seychelles. · Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland. · Imperial College Healthcare NHS Trust, London, United Kingdom. · Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA. · Department of Medicine, University of California Los Angeles, Los Angeles, California, USA. · Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, 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 Psychiatry, University of California, Los Angeles, USA. · Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden. · Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland. · Icelandic Heart Association, Kopavogur, Iceland. · Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. · 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. · Unit of Primary Care, Oulu University Hospital, Oulu, Finland. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland. · Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland. · Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland. · Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland. · National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom. · Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA. · Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland. · Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark. · Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark. · Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland. · Department of Medical Sciences, Uppsala University, Uppsala, Sweden. · Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia. · Synlab Academy, Synlab Services GmbH,Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany. · Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica. · U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France. · Department of Medicine, Kuopio University Hospital, Kuopio, Finland. · Department of Neurology, General Central Hospital, Bolzano, Italy. · Department of Neurology, University of Lübeck, Lübeck, Germany. · Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA. · Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA. · Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland. · Center for Non-Communicable Diseases, Karachi, Pakistan. · Department of Medicine, University of Pennsylvania, USA. · Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland. · South Karelia Central Hospital, Lappeenranta, Finland. · Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany. · Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. · Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland. · Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland. · Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. · Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy. · Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria. · King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia. · Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046. · Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland. · Research Unit, Kuopio University Hospital, Kuopio, Finland. · Department of Medicine, Lausanne University Hospital, Switzerland. · Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands. · Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain. · IMDEA-Alimentacion, Madrid, Spain. · Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. · Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. · Framingham Heart Study, Framingham, MA, USA. · Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA. · Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. · Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. ·Nat Genet · Pubmed #24097068.

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.

11 Article Common variants associated with plasma triglycerides and risk for coronary artery disease. 2013

Do, Ron / Willer, Cristen J / Schmidt, Ellen M / Sengupta, Sebanti / Gao, Chi / Peloso, Gina M / Gustafsson, Stefan / Kanoni, Stavroula / Ganna, Andrea / Chen, Jin / Buchkovich, Martin L / Mora, Samia / Beckmann, Jacques S / Bragg-Gresham, Jennifer L / Chang, Hsing-Yi / Demirkan, Ayşe / Den Hertog, Heleen M / Donnelly, Louise A / Ehret, Georg B / Esko, Tõnu / Feitosa, Mary F / Ferreira, Teresa / Fischer, Krista / Fontanillas, Pierre / Fraser, Ross M / Freitag, Daniel F / Gurdasani, Deepti / Heikkilä, Kauko / Hyppönen, Elina / Isaacs, Aaron / Jackson, Anne U / Johansson, Asa / Johnson, Toby / Kaakinen, Marika / Kettunen, Johannes / Kleber, Marcus E / Li, Xiaohui / Luan, Jian'an / Lyytikäinen, Leo-Pekka / Magnusson, Patrik K E / Mangino, Massimo / Mihailov, Evelin / Montasser, May E / Müller-Nurasyid, Martina / Nolte, Ilja M / O'Connell, Jeffrey R / Palmer, Cameron D / Perola, Markus / Petersen, Ann-Kristin / Sanna, Serena / Saxena, Richa / Service, Susan K / Shah, Sonia / Shungin, Dmitry / Sidore, Carlo / Song, Ci / Strawbridge, Rona J / Surakka, Ida / Tanaka, Toshiko / Teslovich, Tanya M / Thorleifsson, Gudmar / Van den Herik, Evita G / Voight, Benjamin F / Volcik, Kelly A / Waite, Lindsay L / Wong, Andrew / Wu, Ying / Zhang, Weihua / Absher, Devin / Asiki, Gershim / Barroso, Inês / Been, Latonya F / Bolton, Jennifer L / Bonnycastle, Lori L / Brambilla, Paolo / Burnett, Mary S / Cesana, Giancarlo / Dimitriou, Maria / Doney, Alex S F / Döring, Angela / Elliott, Paul / Epstein, Stephen E / Eyjolfsson, Gudmundur Ingi / Gigante, Bruna / Goodarzi, Mark O / Grallert, Harald / Gravito, Martha L / Groves, Christopher J / Hallmans, Göran / Hartikainen, Anna-Liisa / Hayward, Caroline / Hernandez, Dena / Hicks, Andrew A / Holm, Hilma / Hung, Yi-Jen / Illig, Thomas / Jones, Michelle R / Kaleebu, Pontiano / Kastelein, John J P / Khaw, Kay-Tee / Kim, Eric / Klopp, Norman / Komulainen, Pirjo / Kumari, Meena / Langenberg, Claudia / Lehtimäki, Terho / Lin, Shih-Yi / Lindström, Jaana / Loos, Ruth J F / Mach, François / McArdle, Wendy L / Meisinger, Christa / Mitchell, Braxton D / Müller, Gabrielle / Nagaraja, Ramaiah / Narisu, Narisu / Nieminen, Tuomo V M / Nsubuga, Rebecca N / Olafsson, Isleifur / Ong, Ken K / Palotie, Aarno / Papamarkou, Theodore / Pomilla, Cristina / Pouta, Anneli / Rader, Daniel J / Reilly, Muredach P / Ridker, Paul M / Rivadeneira, Fernando / Rudan, Igor / Ruokonen, Aimo / Samani, Nilesh / Scharnagl, Hubert / Seeley, Janet / Silander, Kaisa / Stančáková, Alena / Stirrups, Kathleen / Swift, Amy J / Tiret, Laurence / Uitterlinden, Andre G / van Pelt, L Joost / Vedantam, Sailaja / Wainwright, Nicholas / Wijmenga, Cisca / Wild, Sarah H / Willemsen, Gonneke / Wilsgaard, Tom / Wilson, James F / Young, Elizabeth H / Zhao, Jing Hua / Adair, Linda S / Arveiler, Dominique / Assimes, Themistocles L / Bandinelli, Stefania / Bennett, Franklyn / Bochud, Murielle / Boehm, Bernhard O / Boomsma, Dorret I / Borecki, Ingrid B / Bornstein, Stefan R / Bovet, Pascal / Burnier, Michel / Campbell, Harry / Chakravarti, Aravinda / Chambers, John C / Chen, Yii-Der Ida / Collins, Francis S / Cooper, Richard S / Danesh, John / Dedoussis, George / de Faire, Ulf / Feranil, Alan B / Ferrières, Jean / Ferrucci, Luigi / Freimer, Nelson B / Gieger, Christian / Groop, Leif C / Gudnason, Vilmundur / Gyllensten, Ulf / Hamsten, Anders / Harris, Tamara B / Hingorani, Aroon / Hirschhorn, Joel N / Hofman, Albert / Hovingh, G Kees / Hsiung, Chao Agnes / Humphries, Steve E / Hunt, Steven C / Hveem, Kristian / Iribarren, Carlos / Järvelin, Marjo-Riitta / Jula, Antti / Kähönen, Mika / Kaprio, Jaakko / Kesäniemi, Antero / Kivimaki, Mika / Kooner, Jaspal S / Koudstaal, Peter J / Krauss, Ronald M / Kuh, Diana / Kuusisto, Johanna / Kyvik, Kirsten O / Laakso, Markku / Lakka, Timo A / Lind, Lars / Lindgren, Cecilia M / Martin, Nicholas G / März, Winfried / McCarthy, Mark I / McKenzie, Colin A / Meneton, Pierre / Metspalu, Andres / Moilanen, Leena / Morris, Andrew D / Munroe, Patricia B / Njølstad, Inger / Pedersen, Nancy L / Power, Chris / Pramstaller, Peter P / Price, Jackie F / Psaty, Bruce M / Quertermous, Thomas / Rauramaa, Rainer / Saleheen, Danish / Salomaa, Veikko / Sanghera, Dharambir K / Saramies, Jouko / Schwarz, Peter E H / Sheu, Wayne H-H / Shuldiner, Alan R / Siegbahn, Agneta / Spector, Tim D / Stefansson, Kari / Strachan, David P / Tayo, Bamidele O / Tremoli, Elena / Tuomilehto, Jaakko / Uusitupa, Matti / van Duijn, Cornelia M / Vollenweider, Peter / Wallentin, Lars / Wareham, Nicholas J / Whitfield, John B / Wolffenbuttel, Bruce H R / Altshuler, David / Ordovas, Jose M / Boerwinkle, Eric / Palmer, Colin N A / Thorsteinsdottir, Unnur / Chasman, Daniel I / Rotter, Jerome I / Franks, Paul W / Ripatti, Samuli / Cupples, L Adrienne / Sandhu, Manjinder S / Rich, Stephen S / Boehnke, Michael / Deloukas, Panos / Mohlke, Karen L / Ingelsson, Erik / Abecasis, Goncalo R / Daly, Mark J / Neale, Benjamin M / Kathiresan, Sekar. ·1] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. [4] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. ·Nat Genet · Pubmed #24097064.

ABSTRACT: Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

12 Article Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease. 2013

van Meurs, Joyce B J / Pare, Guillaume / Schwartz, Stephen M / Hazra, Aditi / Tanaka, Toshiko / Vermeulen, Sita H / Cotlarciuc, Ioana / Yuan, Xin / Mälarstig, Anders / Bandinelli, Stefania / Bis, Joshua C / Blom, Henk / Brown, Morris J / Chen, Constance / Chen, Yii-Der / Clarke, Robert J / Dehghan, Abbas / Erdmann, Jeanette / Ferrucci, Luigi / Hamsten, Anders / Hofman, Albert / Hunter, David J / Goel, Anuj / Johnson, Andrew D / Kathiresan, Sekar / Kampman, Ellen / Kiel, Douglas P / Kiemeney, Lambertus A L M / Chambers, John C / Kraft, Peter / Lindemans, Jan / McKnight, Barbara / Nelson, Christopher P / O'Donnell, Christopher J / Psaty, Bruce M / Ridker, Paul M / Rivadeneira, Fernando / Rose, Lynda M / Seedorf, Udo / Siscovick, David S / Schunkert, Heribert / Selhub, Jacob / Ueland, Per M / Vollenweider, Peter / Waeber, Gérard / Waterworth, Dawn M / Watkins, Hugh / Witteman, Jacqueline C M / den Heijer, Martin / Jacques, Paul / Uitterlinden, Andre G / Kooner, Jaspal S / Rader, Dan J / Reilly, Muredach P / Mooser, Vincent / Chasman, Daniel I / Samani, Nilesh J / Ahmadi, Kourosh R. ·Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. ·Am J Clin Nutr · Pubmed #23824729.

ABSTRACT: BACKGROUND: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. OBJECTIVE: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. DESIGN: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10(⁻⁸) were tested for association with CAD in 31,400 cases and 92,927 controls. RESULTS: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 × 10⁻⁹), SLC17A3 (1.0 × 10⁻⁸), GTPB10 (1.7 × 10⁻⁸), CUBN (7.5 × 10⁻¹⁰), HNF1A (1.2 × 10⁻¹²)), and FUT2 (6.6 × 10⁻⁹), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-μmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 × 10⁻³⁶). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). CONCLUSIONS: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD.

13 Article Biological, clinical and population relevance of 95 loci for blood lipids. 2010

Teslovich, Tanya M / Musunuru, Kiran / Smith, Albert V / Edmondson, Andrew C / Stylianou, Ioannis M / Koseki, Masahiro / Pirruccello, James P / Ripatti, Samuli / Chasman, Daniel I / Willer, Cristen J / Johansen, Christopher T / Fouchier, Sigrid W / Isaacs, Aaron / Peloso, Gina M / Barbalic, Maja / Ricketts, Sally L / Bis, Joshua C / Aulchenko, Yurii S / Thorleifsson, Gudmar / Feitosa, Mary F / Chambers, John / Orho-Melander, Marju / Melander, Olle / Johnson, Toby / Li, Xiaohui / Guo, Xiuqing / Li, Mingyao / Shin Cho, Yoon / Jin Go, Min / Jin Kim, Young / Lee, Jong-Young / Park, Taesung / Kim, Kyunga / Sim, Xueling / Twee-Hee Ong, Rick / Croteau-Chonka, Damien C / Lange, Leslie A / Smith, Joshua D / Song, Kijoung / Hua Zhao, Jing / Yuan, Xin / Luan, Jian'an / Lamina, Claudia / Ziegler, Andreas / Zhang, Weihua / Zee, Robert Y L / Wright, Alan F / Witteman, Jacqueline C M / Wilson, James F / Willemsen, Gonneke / Wichmann, H-Erich / Whitfield, John B / Waterworth, Dawn M / Wareham, Nicholas J / Waeber, Gérard / Vollenweider, Peter / Voight, Benjamin F / Vitart, Veronique / Uitterlinden, Andre G / Uda, Manuela / Tuomilehto, Jaakko / Thompson, John R / Tanaka, Toshiko / Surakka, Ida / Stringham, Heather M / Spector, Tim D / Soranzo, Nicole / Smit, Johannes H / Sinisalo, Juha / Silander, Kaisa / Sijbrands, Eric J G / Scuteri, Angelo / Scott, James / Schlessinger, David / Sanna, Serena / Salomaa, Veikko / Saharinen, Juha / Sabatti, Chiara / Ruokonen, Aimo / Rudan, Igor / Rose, Lynda M / Roberts, Robert / Rieder, Mark / Psaty, Bruce M / Pramstaller, Peter P / Pichler, Irene / Perola, Markus / Penninx, Brenda W J H / Pedersen, Nancy L / Pattaro, Cristian / Parker, Alex N / Pare, Guillaume / Oostra, Ben A / O'Donnell, Christopher J / Nieminen, Markku S / Nickerson, Deborah A / Montgomery, Grant W / Meitinger, Thomas / McPherson, Ruth / McCarthy, Mark I / McArdle, Wendy / Masson, David / Martin, Nicholas G / Marroni, Fabio / Mangino, Massimo / Magnusson, Patrik K E / Lucas, Gavin / Luben, Robert / Loos, Ruth J F / Lokki, Marja-Liisa / Lettre, Guillaume / Langenberg, Claudia / Launer, Lenore J / Lakatta, Edward G / Laaksonen, Reijo / Kyvik, Kirsten O / Kronenberg, Florian / König, Inke R / Khaw, Kay-Tee / Kaprio, Jaakko / Kaplan, Lee M / Johansson, Asa / Jarvelin, Marjo-Riitta / Janssens, A Cecile J W / Ingelsson, Erik / Igl, Wilmar / Kees Hovingh, G / Hottenga, Jouke-Jan / Hofman, Albert / Hicks, Andrew A / Hengstenberg, Christian / Heid, Iris M / Hayward, Caroline / Havulinna, Aki S / Hastie, Nicholas D / Harris, Tamara B / Haritunians, Talin / Hall, Alistair S / Gyllensten, Ulf / Guiducci, Candace / Groop, Leif C / Gonzalez, Elena / Gieger, Christian / Freimer, Nelson B / Ferrucci, Luigi / Erdmann, Jeanette / Elliott, Paul / Ejebe, Kenechi G / Döring, Angela / Dominiczak, Anna F / Demissie, Serkalem / Deloukas, Panagiotis / de Geus, Eco J C / de Faire, Ulf / Crawford, Gabriel / Collins, Francis S / Chen, Yii-der I / Caulfield, Mark J / Campbell, Harry / Burtt, Noel P / Bonnycastle, Lori L / Boomsma, Dorret I / Boekholdt, S Matthijs / Bergman, Richard N / Barroso, Inês / Bandinelli, Stefania / Ballantyne, Christie M / Assimes, Themistocles L / Quertermous, Thomas / Altshuler, David / Seielstad, Mark / Wong, Tien Y / Tai, E-Shyong / Feranil, Alan B / Kuzawa, Christopher W / Adair, Linda S / Taylor, Herman A / Borecki, Ingrid B / Gabriel, Stacey B / Wilson, James G / Holm, Hilma / Thorsteinsdottir, Unnur / Gudnason, Vilmundur / Krauss, Ronald M / Mohlke, Karen L / Ordovas, Jose M / Munroe, Patricia B / Kooner, Jaspal S / Tall, Alan R / Hegele, Robert A / Kastelein, John J P / Schadt, Eric E / Rotter, Jerome I / Boerwinkle, Eric / Strachan, David P / Mooser, Vincent / Stefansson, Kari / Reilly, Muredach P / Samani, Nilesh J / Schunkert, Heribert / Cupples, L Adrienne / Sandhu, Manjinder S / Ridker, Paul M / Rader, Daniel J / van Duijn, Cornelia M / Peltonen, Leena / Abecasis, Gonçalo R / Boehnke, Michael / Kathiresan, Sekar. ·Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. ·Nature · Pubmed #20686565.

ABSTRACT: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.