Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Coronary Artery Disease: HELP
Articles by Lenore J. Launer
Based on 18 articles published since 2010
(Why 18 articles?)
||||

Between 2010 and 2020, L. Launer wrote the following 18 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 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 / Anonymous820925 / Anonymous830925 / Anonymous840925 / Anonymous850925 / Anonymous860925 / 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.

2 Article Visit-to-Visit Blood Pressure Variability in Young Adulthood and Hippocampal Volume and Integrity at Middle Age: The CARDIA Study (Coronary Artery Risk Development in Young Adults). 2017

Yano, Yuichiro / Reis, Jared P / Levine, Deborah A / Bryan, R Nick / Viera, Anthony J / Shimbo, Daichi / Tedla, Yacob G / Allen, Norrina B / Schreiner, Pamela J / Bancks, Michael P / Sidney, Stephen / Pletcher, Mark J / Liu, Kiang / Greenland, Philip / Lloyd-Jones, Donald M / Launer, Lenore J. ·From the Department of Preventive Medicine, University of Mississippi Medical Center, Jackson (Y.Y.) · Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (Y.Y., Y.G.T., N.B.A., M.P.B., K.L., P.G., D.M.L.-J.) · Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (J.P.R.) · Division of General Medicine, University of Michigan, Ann Arbor (D.A.L.) · Department of Radiology, University of Pennsylvania Health System, Philadelphia (R.N.B.) · Department of Family Medicine, Hypertension Research Program, University of North Carolina at Chapel Hill (A.J.V.) · Department of Medicine, Columbia University Medical Center, New York, NY (D.S.) · Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (P.J.S.) · Division of Research, Kaiser Permanente of Northern California, Oakland (S.S.) · Department of Epidemiology and Biostatistics, University of California, San Francisco (M.J.P.) · and Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD (L.J.L.). ·Hypertension · Pubmed #28993449.

ABSTRACT: The aims of this study are to assess the relationships of visit-to-visit blood pressure (BP) variability in young adulthood to hippocampal volume and integrity at middle age. We used data over 8 examinations spanning 25 years collected in the CARDIA study (Coronary Artery Risk Development in Young Adults) of black and white adults (age, 18-30 years) started in 1985 to 1986. Visit-to-visit BP variability was defined as by SD

3 Article Allometric scaling of brain regions to intra-cranial volume: An epidemiological MRI study. 2017

de Jong, Laura W / Vidal, Jean-Sébastien / Forsberg, Lars E / Zijdenbos, Alex P / Haight, Thaddeus / Anonymous6151022 / Sigurdsson, Sigurdur / Gudnason, Vilmundur / van Buchem, Mark A / Launer, Lenore J. ·Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. · Geriatrics Department, AP-HP, Broca Hospital, Paris, 75013, France. · Université Paris Descartes, Sorbonne Paris V, Paris, EA, 4468, 75006, France. · Department of Clinical Neuroscience Karolinska Institute, Stockholm, Sweden. · Biospective Inc, Montreal, Quebec, Canada. · Intramural Research Program of the National Institute on Aging, Bethesda, Maryland. · Icelandic Heart Association, Kopavogur, Iceland. ·Hum Brain Mapp · Pubmed #27557999.

ABSTRACT: There is growing evidence that sub-structures of the brain scale allometrically to total brain size, that is, in a non-proportional and non-linear way. Here, scaling of different volumes of interest (VOI) to intra-cranial volume (ICV) was examined. It was assessed whether scaling was allometric or isometric and whether scaling coefficients significantly differed from each other. We also tested to what extent allometric scaling of VOI was introduced by the automated segmentation technique. Furthermore, reproducibility of allometric scaling was studied different age groups and study populations. Study samples included samples of cognitively healthy adults from the community-based Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) (N = 3,883), the Coronary Artery Risk Development in Young Adults Study (CARDIA) (N =709), and the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 180). Data encompassed participants with different age, ethnicity, risk factor profile, and ICV and VOI obtained with different automated MRI segmentation techniques. Our analysis showed that (1) allometric scaling is a trait of all parts of the brain, (2) scaling of neo-cortical white matter, neo-cortical gray matter, and deep gray matter structures including the cerebellum are significantly different from each other, and (3) allometric scaling of brain structures cannot solely be explained by age-associated atrophy, sex, ethnicity, or a systematic bias from study-specific segmentation algorithm, but appears to be a true feature of brain geometry. Hum Brain Mapp 38:151-164, 2017. © 2016 Wiley Periodicals, Inc.

4 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 / Anonymous6351022. · ·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.

5 Article Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium. 2016

Dehghan, Abbas / Bis, Joshua C / White, Charles C / Smith, Albert Vernon / Morrison, Alanna C / Cupples, L Adrienne / Trompet, Stella / Chasman, Daniel I / Lumley, Thomas / Völker, Uwe / Buckley, Brendan M / Ding, Jingzhong / Jensen, Majken K / Folsom, Aaron R / Kritchevsky, Stephen B / Girman, Cynthia J / Ford, Ian / Dörr, Marcus / Salomaa, Veikko / Uitterlinden, André G / Eiriksdottir, Gudny / Vasan, Ramachandran S / Franceschini, Nora / Carty, Cara L / Virtamo, Jarmo / Demissie, Serkalem / Amouyel, Philippe / Arveiler, Dominique / Heckbert, Susan R / Ferrières, Jean / Ducimetière, Pierre / Smith, Nicholas L / Wang, Ying A / Siscovick, David S / Rice, Kenneth M / Wiklund, Per-Gunnar / Taylor, Kent D / Evans, Alun / Kee, Frank / Rotter, Jerome I / Karvanen, Juha / Kuulasmaa, Kari / Heiss, Gerardo / Kraft, Peter / Launer, Lenore J / Hofman, Albert / Markus, Marcello R P / Rose, Lynda M / Silander, Kaisa / Wagner, Peter / Benjamin, Emelia J / Lohman, Kurt / Stott, David J / Rivadeneira, Fernando / Harris, Tamara B / Levy, Daniel / Liu, Yongmei / Rimm, Eric B / Jukema, J Wouter / Völzke, Henry / Ridker, Paul M / Blankenberg, Stefan / Franco, Oscar H / Gudnason, Vilmundur / Psaty, Bruce M / Boerwinkle, Eric / O'Donnell, Christopher J. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States of America. · Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America. · Icelandic Heart Association, Kopavogur, Iceland. · University of Iceland, Reykjavik, Iceland. · Human Genetics Center, and Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, United States of America. · Boston University's and National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, United States of America. · Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. · Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. · Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Department of Biostatistics, University of Washington, Seattle, WA, United States of America. · Department of Statistics, University of Auckland, Auckland, New Zealand. · Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany. · DZHK (German Center for Cardiovascular Research), partner site, Greifswald, Germany. · Department of Pharmacology and Therapeutics, University College, Cork, Ireland. · Department of Internal Medicine, Division of Geriatrics, Wake Forest University, Winston-Salem, North Carolina, United States of America. · Department of Nutrition, Harvard School of Public Health, Boston, MA, United States of America. · Channing Division of Network Medicine, Harvard Medical School, Boston, MA, United States of America. · Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, United States of America. · Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, United States of America. · Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States of America. · Department of Epidemiology, Merck Research Laboratories, Merck Sharp & Dohme Corp., Whitehouse Station, NJ, United States of America. · Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom. · Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany. · National Institute for Health and Welfare, Helsinki, Finland. · Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America. · Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America. · Department of Preventive Medicine, Boston University School of Medicine, Boston, MA, United States of America. · Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States of America. · Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America. · Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France. · Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Strasbourg, France. · Department of Epidemiology, University of Washington, Seattle, WA, United States of America. · Group Health Research Institute, Group Health Cooperative, Seattle, United States of America. · Departments of Cardiology and Epidemiology, Toulouse University Hospital, Toulouse, France. · National Institute of Health and Medical Research (U258), Paris, France. · Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs Office of Research and Development, Seattle, WA, United States of America. · Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA, United States of America. · The New York Academy of Medicine, New York, NY, United States of America. · Department of Medicine, Umeå University Hospital, Umeå, Sweden. · Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, CA, United States of America. · Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, United States of America. · UKCRC Centre of Excellence for Public Health Research (Northern Ireland), Queen's University of Belfast, Belfast, United Kingdom. · Department of Mathematics and Statistics, University of Jyväskylä, Jyväskylä, Finland. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States of America. · Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States of America. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland. · Department of Epidemiology & Prevention, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, United States of America. · Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, United Kingdom. · Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands. · Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands. · Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands. · Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Health Services, University of Washington, Seattle, WA, United States of America. · Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America. · Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, United States of America. · Cardiology Section, Department of Medicine, Boston Veteran's Administration Healthcare, Boston, MA, United States of America. ·PLoS One · Pubmed #26950853.

ABSTRACT: BACKGROUND: Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. METHODS: We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. RESULTS: In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). CONCLUSIONS: QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.

6 Article Association Between Interstitial Lung Abnormalities and All-Cause Mortality. 2016

Putman, Rachel K / Hatabu, Hiroto / Araki, Tetsuro / Gudmundsson, Gunnar / Gao, Wei / Nishino, Mizuki / Okajima, Yuka / Dupuis, Josée / Latourelle, Jeanne C / Cho, Michael H / El-Chemaly, Souheil / Coxson, Harvey O / Celli, Bartolome R / Fernandez, Isis E / Zazueta, Oscar E / Ross, James C / Harmouche, Rola / Estépar, Raúl San José / Diaz, Alejandro A / Sigurdsson, Sigurdur / Gudmundsson, Elías F / Eiríksdottír, Gudny / Aspelund, Thor / Budoff, Matthew J / Kinney, Gregory L / Hokanson, John E / Williams, Michelle C / Murchison, John T / MacNee, William / Hoffmann, Udo / O'Donnell, Christopher J / Launer, Lenore J / Harrris, Tamara B / Gudnason, Vilmundur / Silverman, Edwin K / O'Connor, George T / Washko, George R / Rosas, Ivan O / Hunninghake, Gary M / Anonymous3340858 / Anonymous3350858. ·Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Respiratory Medicine and Sleep, Landspital University Hospital, University of Iceland, Reykjavik, Iceland. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts. · Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts6Department of Radiology, St. Luke's International Hospital, Tokyo, Japan. · Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts7National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. · Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts9Department of Neurology, Boston University, Boston, Massachusetts. · Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts10Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Radiology, University of British Columbia, Vancouver, BC, Canada. · Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts12Comprehensive Pneumology Center, Ludwig-Maximilians-University, University Hospital Grosshadern, Munich, Germany13Helmholtz Zentrum München. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. · Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts14Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts. · Icelandic Heart Association, Kopavogur, Iceland. · Icelandic Heart Association, Kopavogur, Iceland16University of Iceland, Reykjavik, Iceland. · Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California. · Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Denver, Colorado. · University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Edinburgh, Scotland. · Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh, Scotland. · Centre for Inflammation Research, University of Edinburgh, Edinburgh, Scotland. · Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts23Cardiovascular Epidemiology and Human Genomics Branch, NHLBI Division of Intramural Research, Bethesda, Maryland. · Intramural Research Program, National Institute of Aging, NIH, Bethesda, Maryland. · National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts8Pulmonary Center, Department of Medicine, Boston University, Boston, Massachusetts. · Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts3Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. ·JAMA · Pubmed #26881370.

ABSTRACT: IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006). EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS: Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE: In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

7 Article Blood Pressure Reactivity to Psychological Stress in Young Adults and Cognition in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. 2016

Yano, Yuichiro / Ning, Hongyan / Reis, Jared P / Lewis, Cora E / Launer, Lenore J / Bryan, R Nick / Yaffe, Kristine / Sidney, Stephen / Albanese, Emiliano / Greenland, Philip / Lloyd-Jones, Donald / Liu, Kiang. ·Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (Y.Y., H.N., P.G., D.L.J., K.L.). · Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (J.P.R.). · Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, AL (C.E.L.). · Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, MD (L.J.L.). · Department of Radiology, University of Pennsylvania Health System, Philadelphia, PA (N.B.). · Department of Psychiatry, Neurology and Epidemiology, University of California, San Francisco, San Francisco, CA (K.Y.). · Division of Research, Kaiser Permanente Northern California, Oakland, CA (S.S.). · University of Geneva, Switzerland (E.A.). ·J Am Heart Assoc · Pubmed #26764414.

ABSTRACT: BACKGROUND: The classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress-induced BP reactivity in young adults is associated with midlife cognitive function is sparse. METHODS AND RESULTS: We assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty-three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow-up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow-up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: -0.06 [0.02] and -0.05 [0.02]; all P<0.01). SBP reactivity was more consistently associated than diastolic BP reactivity with cognitive function scores. The associations between SBP reactivity and cognitive function were mostly similar between blacks and whites. CONCLUSIONS: Lower psychological stress-induced SBP reactivity in younger adults was associated with lower cognitive function in midlife. BP reactivity to psychological stressors may have different associations with target organs in hypertension.

8 Article Cognitive function in a middle aged cohort is related to higher quality dietary pattern 5 and 25 years earlier: the CARDIA study. 2015

Zhu, N / Jacobs, D R / Meyer, K A / He, K / Launer, L / Reis, J P / Yaffe, K / Sidney, S / Whitmer, R A / Steffen, L M. ·David R. Jacobs, 1300 South 2nd Street, Ste 300, Minneapolis, MN 55454, Phone: 612-624-4196, Fax: 612-624-0315, Email: jacob004@umn.edu. ·J Nutr Health Aging · Pubmed #25560814.

ABSTRACT: BACKGROUND: Preserving cognitive function is an important public health issue. We investigated whether dietary pattern associates with cognitive function in middle-age. METHODS: We studied 2435 participants in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study of black and white men and women aged 18-30 in 1985-86 (year 0, Y0). We hypothesized that a higher A Priori Diet Quality Score, measured at Y0 and Y20, is associated with better cognitive function measured at Y25. The diet score incorporated 46 food groups (each in servings/day) as the sum of quintile ranks of food groups rated beneficial, 0 for food groups rated neutral, and reversed quintile ranks for food groups rated adverse; higher score indicated better diet quality. Y25 cognitive testing included verbal memory (Rey Auditory-Verbal Learning Test (RAVLT)), psychomotor speed (Digit Symbol Substitution Test (DSST)) and executive function (Stroop). RESULTS: Per 10-unit higher diet score at Y20, the RAVLT was 0.32 words recalled higher, the DSST was 1.76 digits higher, and the Stroop was 1.00 seconds+errors lower (better performance) after adjusting for race, sex, age, clinic, and energy intake. Further adjustment for physical activity, smoking, education, and body mass index attenuated the association slightly. Diet score at Y0 and increase in diet score over 20 years were also positively associated with each cognitive test. CONCLUSIONS: A higher quality dietary pattern was associated with better cognitive function 5 years and even 25 years later in apparently healthy middle-aged adults.

9 Article Long-term blood pressure variability throughout young adulthood and cognitive function in midlife: the Coronary Artery Risk Development in Young Adults (CARDIA) study. 2014

Yano, Yuichiro / Ning, Hongyan / Allen, Norrina / Reis, Jared P / Launer, Lenore J / Liu, Kiang / Yaffe, Kristine / Greenland, Philip / Lloyd-Jones, Donald M. ·From the Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL (Y.Y., H.N., N.A., K.L., P.G., D.M.L.-J.) · Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD (J.P.R.) · Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD (L.J.L.) · and Department of Psychiatry, University of California, San Francisco (K.Y.). ·Hypertension · Pubmed #25156174.

ABSTRACT: Whether long-term blood pressure (BP) variability throughout young adulthood is associated with cognitive function in midlife remains uncertain. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA), which recruited healthy young adults aged 18 to 30 years (mean age, 25 years) at baseline (Y(0)), we assessed BP variability by SD and average real variability (ARV) for 25 years (8 visits). Cognitive function was assessed with the Digit Symbol Substitution Test (psychomotor speed test), the Rey Auditory Verbal Learning Test (verbal memory test), and the modified Stroop test (executive function test) at follow-up (Y(25)). At the Y(25) examination, participants (n=2326) had a mean age of 50.4 years, 43% were men, and 40% were black. In multivariable-adjusted linear regression models, higher ARV(SBP), ARV(DBP), and SD(DBP) were significantly associated with lower scores of Digit Symbol Substitution Test (β [SE]: -0.025 [0.006], -0.029 [0.007], and -0.029 [0.007], respectively; all P<0.001) and Rey Auditory Verbal Learning Test (β [SE]: -0.016 [0.006], -0.021 [0.007], and -0.019 [0.007], respectively; all P<0.05) after adjustment for demographic and clinical characteristics and with cumulative exposure to BP through Y(0) to Y(25). Neither SDBP nor ARV(BP) was associated with the Stroop score. The associations between ARV(BP) or SD(BP) and each cognitive function test were similar between blacks and whites except for 1 significant interaction between race and SDS(BP) on the Digit Symbol Substitution Test (P<0.05). Long-term BP variability for 25 years beginning in young adulthood was associated with worse psychomotor speed and verbal memory tests in midlife, independent of cumulative exposure to BP during follow-up.

10 Article Multilocus genetic risk score associates with ischemic stroke in case-control and prospective cohort studies. 2014

Malik, Rainer / Bevan, Steve / Nalls, Michael A / Holliday, Elizabeth G / Devan, William J / Cheng, Yu-Ching / Ibrahim-Verbaas, Carla A / Verhaaren, Benjamin F J / Bis, Joshua C / Joon, Aron Y / de Stefano, Anita L / Fornage, Myriam / Psaty, Bruce M / Ikram, M Arfan / Launer, Lenore J / van Duijn, Cornelia M / Sharma, Pankaj / Mitchell, Braxton D / Rosand, Jonathan / Meschia, James F / Levi, Christopher / Rothwell, Peter M / Sudlow, Cathie / Markus, Hugh S / Seshadri, Sudha / Dichgans, Martin / Anonymous3831022. ·From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.) · Stroke and Dementia Research Centre, St George's University of London, London, United Kingdom (S.B., H.S.M.) · Laboratory of Neurogenetics (M.A.N.) and Laboratory of Epidemiology and Population Sciences (L.J.L.), National Institute on Aging, National Institutes of Health, Bethesda, MD · Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (E.G.H.) and Center for Translational Neuroscience and Mental Health Research (C.L.), University of Newcastle, Callaghan, NSW, Australia · Center for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, New Lambton, NSW, Australia (E.G.H.) · Department of Neurology, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (W.J.D., J.R.) · Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (Y.-C.C., B.D.M.) · Department of Veterans Affairs and Veterans Affairs Medical Center, Baltimore Geriatric Research, Education, and Clinical Center (GRECC), Baltimore, MD (Y.-C.C., B.D.M.) · Department of Epidemiology (C.A.I.-V., B.F.J.V., M.A.I., C.M.v.D.), Department of Neurology (C.A.I.-V., M.A.I.), and Department of Radiology (B.F.J.V., M.A.I.), Erasmus MC University Medical Center, Rotterdam, The Netherlands · Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Medicine (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle, WA · Institute for Molecular Medicine (A.Y.J., M.F.) and Human Genetics Center (M.F.), University of Texas Health Science Center at Houston · Department of Neurology, Boston University School of Medicine, Boston, MA (A.L.d.S., S.S.) · Department of Biostatistics, Boston University School of Public Health, Boston, MA (A.L.d.S.) · The National Heart, Lung and ·Stroke · Pubmed #24436234.

ABSTRACT: BACKGROUND AND PURPOSE: Genome-wide association studies have revealed multiple common variants associated with known risk factors for ischemic stroke (IS). However, their aggregate effect on risk is uncertain. We aimed to generate a multilocus genetic risk score (GRS) for IS based on genome-wide association studies data from clinical-based samples and to establish its external validity in prospective population-based cohorts. METHODS: Three thousand five hundred forty-eight clinic-based IS cases and 6399 controls from the Wellcome Trust Case Control Consortium 2 were used for derivation of the GRS. Subjects from the METASTROKE consortium served as a replication sample. The validation sample consisted of 22 751 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. We selected variants that had reached genome-wide significance in previous association studies on established risk factors for IS. RESULTS: A combined GRS for atrial fibrillation, coronary artery disease, hypertension, and systolic blood pressure significantly associated with IS both in the case-control samples and in the prospective population-based studies. Subjects in the top quintile of the combined GRS had >2-fold increased risk of IS compared with subjects in the lowest quintile. Addition of the combined GRS to a simple model based on sex significantly improved the prediction of IS in the combined clinic-based samples but not in the population-based studies, and there was no significant improvement in net reclassification. CONCLUSIONS: A multilocus GRS based on common variants for established cardiovascular risk factors was significantly associated with IS both in clinic-based samples and in the general population. However, the improvement in clinical risk prediction was found to be small.

11 Article Subclinical atherosclerotic calcification and cognitive functioning in middle-aged adults: the CARDIA study. 2013

Reis, Jared P / Launer, Lenore J / Terry, James G / Loria, Catherine M / Zeki Al Hazzouri, Adina / Sidney, Stephen / Yaffe, Kristine / Jacobs, David R / Whitlow, Christopher T / Zhu, Na / Carr, J Jeffrey. ·Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD, USA. Electronic address: reisjp@mail.nih.gov. ·Atherosclerosis · Pubmed #24125414.

ABSTRACT: OBJECTIVE: Cardiovascular risk factors in middle-age are associated with cognitive impairment and dementia in older age. Less is known about the burden of calcified subclinical atherosclerosis and cognition, especially in midlife. We examined the association of coronary artery and abdominal aortic calcified plaque (CAC and AAC, respectively) with cognitive functioning in middle-aged adults. METHODS: This cross-sectional study included 2510 black and white adults (age: 43-55 years) without heart disease or stroke who completed a year 25 follow-up exam (2010-11) as part of the Coronary Artery Risk Development in Young Adults Study. CAC and AAC were measured with non-contrast computed tomography. Cognition was assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed), Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT) (verbal memory). RESULTS: A greater amount of CAC and AAC was associated with worse performance on each test of cognitive function after adjustment for age, sex, race, education, and study center. Associations were attenuated, but remained significant for the DSST and RAVLT following additional adjustment for vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia, hypertension, and diabetes. Compared to participants without CAC or AAC, those with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST scores (p < 0.05). CONCLUSIONS: In this community-based sample, greater subclinical atherosclerotic calcification was associated with worse psychomotor speed and memory in midlife. These findings underscore the importance of a life course approach to the study of cognitive impairment with aging.

12 Article Coronary artery calcium and physical performance as determinants of mortality in older age: the AGES-Reykjavik Study. 2013

von Bonsdorff, Mikaela B / Groffen, Danielle A I / Vidal, Jean-Sebastien / Rantanen, Taina / Jonsson, Palmi V / Garcia, Melissa / Aspelund, Thor / Eiriksdottir, Gudny / Siggeirsdóttir, Kristin / Launer, Lenore / Gudnason, Vilmundur / Harris, Tamara B / Anonymous2901022. ·Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, MD, USA; Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, Finland. Electronic address: mikaela.vonbonsdorff@jyu.fi. ·Int J Cardiol · Pubmed #23414742.

ABSTRACT: BACKGROUND: Coronary artery calcium (CAC) and physical performance have been shown to be associated with mortality, but it is not clear whether one of them modifies the association. We investigated the association between the extent of CAC and physical performance among older individuals and explored these individual and combined effects on cardiovascular disease (CVD) mortality and non-CVD mortality. METHODS: We studied 4074 participants of the AGES-Reykjavik Study who were free from coronary heart disease, had a CAC score calculated from computed tomography scans and had data on mobility limitations and gait speed at baseline in 2002-2006 at a mean age of 76 years. Register-based mortality was available until 2009. RESULTS: Odds for mobility limitation and slow gait increased according to the extent of CAC. Altogether 645 persons died during the follow-up. High CAC, mobility limitation and slow gait were independent predictors of CVD mortality and non-CVD mortality. The joint effect of CAC and gait speed on non-CVD mortality was synergistic, i.e. compared to having low CAC and normal gait, the joint effect of high CAC and slow gait exceeded the additive effect of these individual exposures on non-CVD mortality. For CVD mortality, the effect was additive i.e. the joint effect of high CAC and slow gait did not exceed the sum of the individual exposures. CONCLUSIONS: The extent of CAC and decreased physical performance were independent predictors of mortality and the joint presence of these risk factors increased the risk of non-CVD mortality above and beyond the individual effects.

13 Article Coronary artery calcium distributions in older persons in the AGES-Reykjavik study. 2012

Gudmundsson, Elias Freyr / Gudnason, Vilmundur / Sigurdsson, Sigurdur / Launer, Lenore J / Harris, Tamara B / Aspelund, Thor. ·Icelandic Heart Association, Research Institute, Kopavogur, Iceland. ·Eur J Epidemiol · Pubmed #22990371.

ABSTRACT: Coronary Artery Calcium (CAC) is a sign of advanced atherosclerosis and an independent risk factor for cardiac events. Here, we describe CAC-distributions in an unselected aged population and compare modelling methods to characterize CAC-distribution. CAC is difficult to model because it has a skewed and zero inflated distribution with over-dispersion. Data are from the AGES-Reykjavik sample, a large population based study [2002-2006] in Iceland of 5,764 persons aged 66-96 years. Linear regressions using logarithmic- and Box-Cox transformations on CAC+1, quantile regression and a Zero-Inflated Negative Binomial model (ZINB) were applied. Methods were compared visually and with the PRESS-statistic, R(2) and number of detected associations with concurrently measured variables. There were pronounced differences in CAC according to sex, age, history of coronary events and presence of plaque in the carotid artery. Associations with conventional coronary artery disease (CAD) risk factors varied between the sexes. The ZINB model provided the best results with respect to the PRESS-statistic, R(2), and predicted proportion of zero scores. The ZINB model detected similar numbers of associations as the linear regression on ln(CAC+1) and usually with the same risk factors.

14 Article Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. 2011

O'Donnell, Christopher J / Kavousi, Maryam / Smith, Albert V / Kardia, Sharon L R / Feitosa, Mary F / Hwang, Shih-Jen / Sun, Yan V / Province, Michael A / Aspelund, Thor / Dehghan, Abbas / Hoffmann, Udo / Bielak, Lawrence F / Zhang, Qunyuan / Eiriksdottir, Gudny / van Duijn, Cornelia M / Fox, Caroline S / de Andrade, Mariza / Kraja, Aldi T / Sigurdsson, Sigurdur / Elias-Smale, Suzette E / Murabito, Joanne M / Launer, Lenore J / van der Lugt, Aad / Kathiresan, Sekar / Anonymous2040712 / Krestin, Gabriel P / Herrington, David M / Howard, Timothy D / Liu, Yongmei / Post, Wendy / Mitchell, Braxton D / O'Connell, Jeffrey R / Shen, Haiqing / Shuldiner, Alan R / Altshuler, David / Elosua, Roberto / Salomaa, Veikko / Schwartz, Stephen M / Siscovick, David S / Voight, Benjamin F / Bis, Joshua C / Glazer, Nicole L / Psaty, Bruce M / Boerwinkle, Eric / Heiss, Gerardo / Blankenberg, Stefan / Zeller, Tanja / Wild, Philipp S / Schnabel, Renate B / Schillert, Arne / Ziegler, Andreas / Münzel, Thomas F / White, Charles C / Rotter, Jerome I / Nalls, Michael / Oudkerk, Matthijs / Johnson, Andrew D / Newman, Anne B / Uitterlinden, Andre G / Massaro, Joseph M / Cunningham, Julie / Harris, Tamara B / Hofman, Albert / Peyser, Patricia A / Borecki, Ingrid B / Cupples, L Adrienne / Gudnason, Vilmundur / Witteman, Jacqueline C M. ·MPH, NHLBI's Framingham Heart Study, 73 Mount Wayte Ave, Suite 2, Framingham, MA 01702, USA. odonnellc@nhlbi.nih.gov ·Circulation · Pubmed #22144573.

ABSTRACT: BACKGROUND: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI. METHODS AND RESULTS: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene). CONCLUSIONS: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

15 Article Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. 2011

Anonymous650705 / Ehret, Georg B / Munroe, Patricia B / Rice, Kenneth M / Bochud, Murielle / Johnson, Andrew D / Chasman, Daniel I / Smith, Albert V / Tobin, Martin D / Verwoert, Germaine C / Hwang, Shih-Jen / Pihur, Vasyl / Vollenweider, Peter / O'Reilly, Paul F / Amin, Najaf / Bragg-Gresham, Jennifer L / Teumer, Alexander / Glazer, Nicole L / Launer, Lenore / Zhao, Jing Hua / Aulchenko, Yurii / Heath, Simon / Sõber, Siim / Parsa, Afshin / Luan, Jian'an / Arora, Pankaj / Dehghan, Abbas / Zhang, Feng / Lucas, Gavin / Hicks, Andrew A / Jackson, Anne U / Peden, John F / Tanaka, Toshiko / Wild, Sarah H / Rudan, Igor / Igl, Wilmar / Milaneschi, Yuri / Parker, Alex N / Fava, Cristiano / Chambers, John C / Fox, Ervin R / Kumari, Meena / Go, Min Jin / van der Harst, Pim / Kao, Wen Hong Linda / Sjögren, Marketa / Vinay, D G / Alexander, Myriam / Tabara, Yasuharu / Shaw-Hawkins, Sue / Whincup, Peter H / Liu, Yongmei / Shi, Gang / Kuusisto, Johanna / Tayo, Bamidele / Seielstad, Mark / Sim, Xueling / Nguyen, Khanh-Dung Hoang / Lehtimäki, Terho / Matullo, Giuseppe / Wu, Ying / Gaunt, Tom R / Onland-Moret, N Charlotte / Cooper, Matthew N / Platou, Carl G P / Org, Elin / Hardy, Rebecca / Dahgam, Santosh / Palmen, Jutta / Vitart, Veronique / Braund, Peter S / Kuznetsova, Tatiana / Uiterwaal, Cuno S P M / Adeyemo, Adebowale / Palmas, Walter / Campbell, Harry / Ludwig, Barbara / Tomaszewski, Maciej / Tzoulaki, Ioanna / Palmer, Nicholette D / Anonymous660705 / Anonymous670705 / Anonymous680705 / Anonymous690705 / Anonymous700705 / Aspelund, Thor / Garcia, Melissa / Chang, Yen-Pei C / O'Connell, Jeffrey R / Steinle, Nanette I / Grobbee, Diederick E / Arking, Dan E / Kardia, Sharon L / Morrison, Alanna C / Hernandez, Dena / Najjar, Samer / McArdle, Wendy L / Hadley, David / Brown, Morris J / Connell, John M / Hingorani, Aroon D / Day, Ian N M / Lawlor, Debbie A / Beilby, John P / Lawrence, Robert W / Clarke, Robert / Hopewell, Jemma C / Ongen, Halit / Dreisbach, Albert W / Li, Yali / Young, J Hunter / Bis, Joshua C / Kähönen, Mika / Viikari, Jorma / Adair, Linda S / Lee, Nanette R / Chen, Ming-Huei / Olden, Matthias / Pattaro, Cristian / Bolton, Judith A Hoffman / Köttgen, Anna / Bergmann, Sven / Mooser, Vincent / Chaturvedi, Nish / Frayling, Timothy M / Islam, Muhammad / Jafar, Tazeen H / Erdmann, Jeanette / Kulkarni, Smita R / Bornstein, Stefan R / Grässler, Jürgen / Groop, Leif / Voight, Benjamin F / Kettunen, Johannes / Howard, Philip / Taylor, Andrew / Guarrera, Simonetta / Ricceri, Fulvio / Emilsson, Valur / Plump, Andrew / Barroso, Inês / Khaw, Kay-Tee / Weder, Alan B / Hunt, Steven C / Sun, Yan V / Bergman, Richard N / Collins, Francis S / Bonnycastle, Lori L / Scott, Laura J / Stringham, Heather M / Peltonen, Leena / Perola, Markus / Vartiainen, Erkki / Brand, Stefan-Martin / Staessen, Jan A / Wang, Thomas J / Burton, Paul R / Soler Artigas, Maria / Dong, Yanbin / Snieder, Harold / Wang, Xiaoling / Zhu, Haidong / Lohman, Kurt K / Rudock, Megan E / Heckbert, Susan R / Smith, Nicholas L / Wiggins, Kerri L / Doumatey, Ayo / Shriner, Daniel / Veldre, Gudrun / Viigimaa, Margus / Kinra, Sanjay / Prabhakaran, Dorairaj / Tripathy, Vikal / Langefeld, Carl D / Rosengren, Annika / Thelle, Dag S / Corsi, Anna Maria / Singleton, Andrew / Forrester, Terrence / Hilton, Gina / McKenzie, Colin A / Salako, Tunde / Iwai, Naoharu / Kita, Yoshikuni / Ogihara, Toshio / Ohkubo, Takayoshi / Okamura, Tomonori / Ueshima, Hirotsugu / Umemura, Satoshi / Eyheramendy, Susana / Meitinger, Thomas / Wichmann, H-Erich / Cho, Yoon Shin / Kim, Hyung-Lae / Lee, Jong-Young / Scott, James / Sehmi, Joban S / Zhang, Weihua / Hedblad, Bo / Nilsson, Peter / Smith, George Davey / Wong, Andrew / Narisu, Narisu / Stančáková, Alena / Raffel, Leslie J / Yao, Jie / Kathiresan, Sekar / O'Donnell, Christopher J / Schwartz, Stephen M / Ikram, M Arfan / Longstreth, W T / Mosley, Thomas H / Seshadri, Sudha / Shrine, Nick R G / Wain, Louise V / Morken, Mario A / Swift, Amy J / Laitinen, Jaana / Prokopenko, Inga / Zitting, Paavo / Cooper, Jackie A / Humphries, Steve E / Danesh, John / Rasheed, Asif / Goel, Anuj / Hamsten, Anders / Watkins, Hugh / Bakker, Stephan J L / van Gilst, Wiek H / Janipalli, Charles S / Mani, K Radha / Yajnik, Chittaranjan S / Hofman, Albert / Mattace-Raso, Francesco U S / Oostra, Ben A / Demirkan, Ayse / Isaacs, Aaron / Rivadeneira, Fernando / Lakatta, Edward G / Orru, Marco / Scuteri, Angelo / Ala-Korpela, Mika / Kangas, Antti J / Lyytikäinen, Leo-Pekka / Soininen, Pasi / Tukiainen, Taru / Würtz, Peter / Ong, Rick Twee-Hee / Dörr, Marcus / Kroemer, Heyo K / Völker, Uwe / Völzke, Henry / Galan, Pilar / Hercberg, Serge / Lathrop, Mark / Zelenika, Diana / Deloukas, Panos / Mangino, Massimo / Spector, Tim D / Zhai, Guangju / Meschia, James F / Nalls, Michael A / Sharma, Pankaj / Terzic, Janos / Kumar, M V Kranthi / Denniff, Matthew / Zukowska-Szczechowska, Ewa / Wagenknecht, Lynne E / Fowkes, F Gerald R / Charchar, Fadi J / Schwarz, Peter E H / Hayward, Caroline / Guo, Xiuqing / Rotimi, Charles / Bots, Michiel L / Brand, Eva / Samani, Nilesh J / Polasek, Ozren / Talmud, Philippa J / Nyberg, Fredrik / Kuh, Diana / Laan, Maris / Hveem, Kristian / Palmer, Lyle J / van der Schouw, Yvonne T / Casas, Juan P / Mohlke, Karen L / Vineis, Paolo / Raitakari, Olli / Ganesh, Santhi K / Wong, Tien Y / Tai, E Shyong / Cooper, Richard S / Laakso, Markku / Rao, Dabeeru C / Harris, Tamara B / Morris, Richard W / Dominiczak, Anna F / Kivimaki, Mika / Marmot, Michael G / Miki, Tetsuro / Saleheen, Danish / Chandak, Giriraj R / Coresh, Josef / Navis, Gerjan / Salomaa, Veikko / Han, Bok-Ghee / Zhu, Xiaofeng / Kooner, Jaspal S / Melander, Olle / Ridker, Paul M / Bandinelli, Stefania / Gyllensten, Ulf B / Wright, Alan F / Wilson, James F / Ferrucci, Luigi / Farrall, Martin / Tuomilehto, Jaakko / Pramstaller, Peter P / Elosua, Roberto / Soranzo, Nicole / Sijbrands, Eric J G / Altshuler, David / Loos, Ruth J F / Shuldiner, Alan R / Gieger, Christian / Meneton, Pierre / Uitterlinden, Andre G / Wareham, Nicholas J / Gudnason, Vilmundur / Rotter, Jerome I / Rettig, Rainer / Uda, Manuela / Strachan, David P / Witteman, Jacqueline C M / Hartikainen, Anna-Liisa / Beckmann, Jacques S / Boerwinkle, Eric / Vasan, Ramachandran S / Boehnke, Michael / Larson, Martin G / Järvelin, Marjo-Riitta / Psaty, Bruce M / Abecasis, Gonçalo R / Chakravarti, Aravinda / Elliott, Paul / van Duijn, Cornelia M / Newton-Cheh, Christopher / Levy, Daniel / Caulfield, Mark J / Johnson, Toby. · ·Nature · Pubmed #21909115.

ABSTRACT: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

16 Article Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. 2011

Bis, Joshua C / Kavousi, Maryam / Franceschini, Nora / Isaacs, Aaron / Abecasis, Gonçalo R / Schminke, Ulf / Post, Wendy S / Smith, Albert V / Cupples, L Adrienne / Markus, Hugh S / Schmidt, Reinhold / Huffman, Jennifer E / Lehtimäki, Terho / Baumert, Jens / Münzel, Thomas / Heckbert, Susan R / Dehghan, Abbas / North, Kari / Oostra, Ben / Bevan, Steve / Stoegerer, Eva-Maria / Hayward, Caroline / Raitakari, Olli / Meisinger, Christa / Schillert, Arne / Sanna, Serena / Völzke, Henry / Cheng, Yu-Ching / Thorsson, Bolli / Fox, Caroline S / Rice, Kenneth / Rivadeneira, Fernando / Nambi, Vijay / Halperin, Eran / Petrovic, Katja E / Peltonen, Leena / Wichmann, H Erich / Schnabel, Renate B / Dörr, Marcus / Parsa, Afshin / Aspelund, Thor / Demissie, Serkalem / Kathiresan, Sekar / Reilly, Muredach P / Taylor, Kent / Uitterlinden, Andre / Couper, David J / Sitzer, Matthias / Kähönen, Mika / Illig, Thomas / Wild, Philipp S / Orru, Marco / Lüdemann, Jan / Shuldiner, Alan R / Eiriksdottir, Gudny / White, Charles C / Rotter, Jerome I / Hofman, Albert / Seissler, Jochen / Zeller, Tanja / Usala, Gianluca / Ernst, Florian / Launer, Lenore J / D'Agostino, Ralph B / O'Leary, Daniel H / Ballantyne, Christie / Thiery, Joachim / Ziegler, Andreas / Lakatta, Edward G / Chilukoti, Ravi Kumar / Harris, Tamara B / Wolf, Philip A / Psaty, Bruce M / Polak, Joseph F / Li, Xia / Rathmann, Wolfgang / Uda, Manuela / Boerwinkle, Eric / Klopp, Norman / Schmidt, Helena / Wilson, James F / Viikari, Jorma / Koenig, Wolfgang / Blankenberg, Stefan / Newman, Anne B / Witteman, Jacqueline / Heiss, Gerardo / Duijn, Cornelia van / Scuteri, Angelo / Homuth, Georg / Mitchell, Braxton D / Gudnason, Vilmundur / O'Donnell, Christopher J / Anonymous560705. ·Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, USA. joshbis@uw.edu ·Nat Genet · Pubmed #21909108.

ABSTRACT: Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.

17 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.

18 Article Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study. 2010

Vidal, Jean-Sébastien / Sigurdsson, Sigurdur / Jonsdottir, Maria K / Eiriksdottir, Gudny / Thorgeirsson, Gudmundur / Kjartansson, Olafur / Garcia, Melissa E / van Buchem, Mark A / Harris, Tamara B / Gudnason, Vilmundur / Launer, Lenore J. ·National Institutes of Health, NIA/LEDB, 7201 Wisconsin Ave, Gateway Building, Suite 3C309, Bethesda, MD 20892-9205, USA. ·Stroke · Pubmed #20360538.

ABSTRACT: BACKGROUND AND PURPOSE: Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function. METHODS: This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function. RESULTS: Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes. CONCLUSIONS: In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology.