106 results on '"Infectious diseases division, Department of internal medicine"'
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2. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
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Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Munn-Chernoff, M. A., Johnson, E. C., Chou, Y. -L., Coleman, J. R. I., Thornton, L. M., Walters, R. K., Yilmaz, Z., Baker, J. H., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, P., Hanscombe, K. B., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Berrettini, W. H., Boehm, I., Boni, C., Boraska Perica, V., Buehren, K., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Cone, R. D., Courtet, P., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L. E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, M., Foretova, L., Forstner, A. J., Forzan, M., Franklin, C. S., Gallinger, S., Giegling, I., Giuranna, J., Gonidakis, F., Gorwood, P., Gratacos Mayora, M., Guillaume, S., Guo, Y., Hakonarson, H., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S. G., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K. L., Knudsen, G. P. S., La Via, M. C., Le Hellard, S., Levitan, R. D., Li, D., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P. J., Maj, M., Mannik, K., Marsal, S., Marshall, C. R., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, K., Monteleone, A. M., Monteleone, P., Nacmias, B., Navratilova, M., Ntalla, I., O'Toole, J. K., Ophoff, R. A., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Swiatkowska, B., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Walton, E., Widen, E., Zeggini, E., Zerwas, S., Zipfel, S., Bergen, A. W., Boden, J. M., Brandt, H., Crawford, S., Halmi, K. A., Horwood, L. J., Johnson, C., Kaplan, A. S., Kaye, W. H., Mitchell, J., Olsen, C. M., Pearson, J. F., Pedersen, N. L., Strober, M., Werge, T., Whiteman, D. C., Woodside, D. B., Grove, J., Henders, A. K., Larsen, J. T., Parker, R., Petersen, L. V., Jordan, J., Kennedy, M. A., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Mortensen, P. B., Polimanti, R., Mcclintick, J. N., Adkins, A. E., Aliev, F., Bacanu, S. -A., Batzler, A., Bertelsen, S., Biernacka, J. M., Bigdeli, T. B., Chen, L. -S., Clarke, T. -K., Degenhardt, F., Docherty, A. R., Edwards, A. C., Foo, J. C., Fox, L., Frank, J., Hack, L. M., Hartmann, A. M., Hartz, S. M., Heilmann-Heimbach, S., Hodgkinson, C., Hoffmann, P., Hottenga, J. -J., Konte, B., Lahti, J., Lahti-Pulkkinen, M., Lai, D., Ligthart, L., Loukola, A., Maher, B. S., Mbarek, H., Mcintosh, A. M., Mcqueen, M. B., Meyers, J. L., Milaneschi, Y., Palviainen, T., Peterson, R. E., Ryu, E., Saccone, N. L., Salvatore, J. E., Sanchez-Roige, S., Schwandt, M., Sherva, R., Streit, F., Strohmaier, J., Thomas, N., Wang, J. -C., Webb, B. T., Wedow, R., Wetherill, L., Wills, A. G., Zhou, H., Boardman, J. D., Chen, D., Choi, D. -S., Copeland, W. E., Culverhouse, R. C., Dahmen, N., Degenhardt, L., Domingue, B. W., Frye, M. A., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, K., Reynolds, M. D., Ridinger, M., Scherbaum, N., Schuckit, M. A., Soyka, M., Treutlein, J., Witt, S. H., Wodarz, N., Zill, P., Adkins, D. E., Boomsma, D. I., Bierut, L. J., Brown, S. A., Bucholz, K. K., Costello, E. J., de Wit, H., Diazgranados, N., Eriksson, J. G., Farrer, L. A., Foroud, T. M., Gillespie, N. A., Goate, A. M., Goldman, D., Grucza, R. A., Hancock, D. B., Harris, K. M., Hesselbrock, V., Hewitt, J. K., Hopfer, C. J., Iacono, W. G., Johnson, E. O., Karpyak, V. M., Kendler, K. S., Kranzler, H. R., Krauter, K., Lind, P. A., Mcgue, M., Mackillop, J., Madden, P. A. F., Maes, H. H., Magnusson, P. K. E., Nelson, E. C., Nothen, M. M., Palmer, A. A., Penninx, B. W. J. H., Porjesz, B., Rice, J. P., Rietschel, M., Riley, B. P., Rose, R. J., Shen, P. -H., Silberg, J., Stallings, M. C., Tarter, R. E., Vanyukov, M. M., Vrieze, S., Wall, T. L., Whitfield, J. B., Zhao, H., Neale, B. M., Wade, T. D., Heath, A. C., Montgomery, G. W., Martin, N. G., Sullivan, P. F., Kaprio, J., Breen, G., Gelernter, J., Edenberg, H. J., Bulik, C. M., and Agrawal, A.
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Netherlands Twin Register (NTR) ,Alcoholism/genetics ,Schizophrenia/genetics ,[SDV]Life Sciences [q-bio] ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Medizin ,Medicine (miscellaneous) ,Genome-wide association study ,Alcohol use disorder ,Anorexia nervosa ,Linkage Disequilibrium ,ddc:616.89 ,[SCCO]Cognitive science ,0302 clinical medicine ,Risk Factors ,Tobacco Use Disorder/genetics ,Substance-Related Disorders/genetics ,0303 health sciences ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Factors de risc en les malalties ,Bulimia nervosa ,Feeding and Eating Disorders/genetics ,eating disorders ,genetic correlation ,substance use ,Tobacco Use Disorder ,3. Good health ,Fenotip ,[SDV] Life Sciences [q-bio] ,Psychiatry and Mental health ,Alcoholism ,Eating disorders ,Phenotype ,Schizophrenia ,Drinking of alcoholic beverages ,eating disorder ,Consum d'alcohol ,Major depressive disorder ,medicine.symptom ,Depressive Disorder, Major/genetics ,eating disorders, genetic correlation, substance use ,Clinical psychology ,Substance abuse ,Risk factors in diseases ,Substance-Related Disorders ,Polymorphism, Single Nucleotide ,Article ,Feeding and Eating Disorders ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,mental disorders ,Genetics ,medicine ,Humans ,Trastorns de la conducta alimentària ,030304 developmental biology ,Genetic association ,Pharmacology ,Depressive Disorder, Major ,Binge eating ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,[SCCO] Cognitive science ,medicine.disease ,Comorbidity ,Twin study ,030227 psychiatry ,Abús de substàncies ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,business ,Genètica ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Genome-Wide Association Study - Abstract
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa (BN) and problem alcohol use (genetic correlation [rg], twin-based=0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge-eating, AN without binge-eating, and a BN factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder (MDD). Total sample sizes per phenotype ranged from ~2,400 to ~537,000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg=0.18; false discovery rate q=0.0006), cannabis initiation and AN (rg=0.23; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs
- Published
- 2021
3. Associations of autozygosity with a broad range of human phenotypes
- Author
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Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. F., Læknadeild (HÍ), Faculty of Medicine (UI), Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ), Faculty of Sociology, Anthropology and Folkloristics (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Háskóli Íslands, University of Iceland, Clark, David W [0000-0002-1025-9185], Okada, Yukinori [0000-0002-0311-8472], Moore, Kristjan H S [0000-0002-9579-4362], Mason, Dan [0000-0002-0026-9216], Pirastu, Nicola [0000-0002-5363-3886], Gandin, Ilaria [0000-0003-3196-2491], Deelen, Patrick [0000-0002-5654-3966], Schurmann, Claudia [0000-0003-4158-9192], Medina-Gomez, Carolina [0000-0001-7999-5538], Karlsson, Robert [0000-0002-8949-2587], Bao, Yanchun [0000-0002-6102-5098], Biino, Ginevra [0000-0002-9936-946X], Brumat, Marco [0000-0003-3268-039X], Chai, Jin-Fang [0000-0003-3770-1137], Eccles, David A [0000-0003-4634-4995], Gordon, Scott 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[0000-0002-3352-4500], Cocca, Massimiliano [0000-0002-1127-7596], Collins, Francis S [0000-0002-1023-7410], Cugliari, Giovanni [0000-0002-6080-0718], Damulina, Anna [0000-0001-8241-2727], Day, Felix R [0000-0003-3789-7651], Dhana, Klodian [0000-0002-6397-7009], Dzimiri, Nduna [0000-0003-3395-5754], Elliott, Paul [0000-0002-7511-5684], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Girotto, Giorgia [0000-0003-4507-6589], Goel, Anuj [0000-0003-2307-4021], Goodarzi, Mark O [0000-0001-6364-5103], Gudbjartsson, Daniel F [0000-0002-5222-9857], Guity, Kamran [0000-0002-8379-9668], van Heel, David A [0000-0002-0637-2265], Hirata, Makoto [0000-0002-9994-9958], Ikram, M Arfan [0000-0003-0372-8585], Kamatani, Yoichiro [0000-0001-8748-5597], Kanai, Masahiro [0000-0001-5165-4408], Khor, Chiea Chuen [0000-0002-1128-4729], Kolcic, Ivana [0000-0001-7918-6052], Langenberg, Claudia [0000-0002-5017-7344], Lawlor, Deborah A [0000-0002-6793-2262], Liu, Jianjun [0000-0002-3255-3019], London, Stephanie J [0000-0003-4911-5290], Luan, Jian’an [0000-0003-3137-6337], Matoba, Nana [0000-0001-5329-0134], Mei, Xue W [0000-0002-6279-4884], Mezzavilla, Massimo [0000-0002-9000-4595], Milani, Lili [0000-0002-5323-3102], Mori, Trevor A [0000-0002-5264-9229], Murakami, Yoshinori [0000-0002-2826-4396], Murray, Alison D [0000-0003-4915-4847], Mychaleckyj, Josyf C [0000-0003-2595-0005], Neville, Matt J [0000-0002-6004-5433], Nolte, Ilja M [0000-0001-5047-4077], Ong, Ken K [0000-0003-4689-7530], Pálsson, Gunnar [0000-0002-8231-3961], Pankow, James S [0000-0001-7076-483X], Pattaro, Cristian [0000-0002-4119-0109], Quintana-Murci, Lluis [0000-0003-2429-6320], van Rheenen, Wouter [0000-0002-5860-1533], Rich, Stephen S [0000-0003-3872-7793], Rietveld, Cornelius A [0000-0003-4053-1861], Ruggiero, Daniela [0000-0003-3898-7827], Sabanayagam, Charumathi [0000-0002-4042-4719], Sabater-Lleal, Maria [0000-0002-0128-379X], Sala, Cinzia Felicita [0000-0003-2514-2075], Salomaa, Veikko [0000-0001-7563-5324], Scott, Laura J [0000-0002-4886-5084], Sedaghati-Khayat, Bahareh [0000-0002-7665-8648], Sennblad, Bengt [0000-0002-4360-8003], van Setten, Jessica [0000-0002-4934-7510], Smith, Blair H [0000-0002-5362-9430], Stančáková, Alena [0000-0002-1375-0252], Stanton, Alice [0000-0002-4961-165X], Straker, Leon [0000-0002-7786-4128], Sulem, Patrick [0000-0001-7123-6123], Swertz, Morris A [0000-0002-0979-3401], Taylor, Kent D [0000-0002-2756-4370], Tzoulaki, Ioanna [0000-0002-4275-9328], Veldink, Jan H [0000-0001-5572-9657], Vitart, Veronique [0000-0002-4991-3797], Völker, Uwe [0000-0002-5689-3448], Wander, Gurpreet S [0000-0002-4596-4247], Wang, Ya Xing [0000-0003-2749-7793], Wild, Sarah [0000-0001-7824-2569], Yuan, Jian-Min [0000-0002-4620-3108], Asselbergs, Folkert W [0000-0002-1692-8669], Boehnke, Mike [0000-0002-6442-7754], Bouchard, Claude [0000-0002-0048-491X], Brody, Jennifer A [0000-0001-8509-148X], Campbell, Archie [0000-0003-0198-5078], Caulfield, Mark J [0000-0001-9295-3594], Smith, George Davey [0000-0002-1407-8314], Dorajoo, Rajkumar [0000-0001-6608-2051], Ellinghaus, David [0000-0002-4332-6110], Erdmann, Jeanette [0000-0002-4486-6231], Evangelou, Evangelos [0000-0002-5488-2999], Feenstra, Bjarke [0000-0003-1478-649X], Feitosa, Mary [0000-0002-0933-2410], Franke, Andre [0000-0003-1530-5811], Grant, Struan F A [0000-0003-2025-5302], Griffiths, Lyn R [0000-0002-6774-5475], Groop, Leif [0000-0002-0187-3263], Gudnason, Vilmundur [0000-0001-5696-0084], van der Harst, Pim [0000-0002-2713-686X], Heng, Chew-Kiat [0000-0002-7309-9473], Hicks, Andrew A [0000-0001-6320-0411], Jaddoe, Vincent W V [0000-0003-2939-0041], De Jager, Philip L [0000-0002-8057-2505], Johannesson, Magnus [0000-0001-8759-6393], Johansson, Åsa [0000-0002-2915-4498], Jonas, Jost B [0000-0003-2972-5227], Jukema, J Wouter [0000-0002-3246-8359], Kaprio, Jaakko [0000-0002-3716-2455], Laakso, Markku [0000-0002-3394-7749], van der Laan, Sander W [0000-0001-6888-1404], Lahti, Jari [0000-0002-4310-5297], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Merriman, Tony R [0000-0003-0844-8726], Metspalu, Andres [0000-0002-3718-796X], Mohlke, Karen L [0000-0001-6721-153X], Montgomery, Grant W [0000-0002-4140-8139], Munroe, Patricia B [0000-0002-4176-2947], Nyholt, Dale R [0000-0001-7159-3040], Ober, Carole [0000-0003-4626-9809], Oldehinkel, Albertine J [0000-0003-3925-3913], Palmer, Colin [0000-0002-6415-6560], Perusse, Louis [0000-0001-6440-9698], Polderman, Tinca J. C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
- Subjects
0301 basic medicine ,631/208/1397 ,Chemistry(all) ,Health Status ,[SDV]Life Sciences [q-bio] ,LOCI ,General Physics and Astronomy ,MESH: Haplotype ,MESH: Cognition ,030105 genetics & heredity ,Runs of Homozygosity ,Biochemistry ,Consanguinity ,Cognition ,Inbreeding depression ,2.1 Biological and endogenous factors ,Body Size ,Inbreeding ,Skyldleikarækt ,Aetiology ,Human phenotypes ,lcsh:Science ,MESH: Health Status ,Genetics ,Multidisciplinary ,Inbreeding Depression ,Confounding ,Homozygote ,RUNS ,631/208/205 ,631/208/721 ,3. Good health ,genomic inbreeding coefficients ,MESH: Risk-Taking ,631/208/730 ,Autozygosit ,homozygosity ,Erfðarannsóknir ,Medical Genetics ,genomic inbreeding coefficient ,MESH: Homozygote ,Offspring ,Science ,Autozygosity ,Blóðsifjar ,610 Medicine & health ,Biology ,INBREEDING DEPRESSION ,HOMOZYGOSITY ,FERTILITY ,QUANTIFICATION ,Physics and Astronomy(all) ,General Biochemistry, Genetics and Molecular Biology ,Article ,Association ,03 medical and health sciences ,Risk-Taking ,360 Social problems & social services ,Journal Article ,Humans ,ddc:610 ,Allele ,Alleles ,Medicinsk genetik ,Genetic association study ,MESH: Consanguinity ,MESH: Body Size ,MESH: Humans ,Biochemistry, Genetics and Molecular Biology(all) ,MESH: Alleles ,Haplotype ,MESH: Fertility ,General Chemistry ,Brain Disorders ,MESH: Inbreeding Depression ,030104 developmental biology ,Fertility ,Haplotypes ,Genetic markers ,lcsh:Q ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,3111 Biomedicine ,Genetics and Molecular Biology(all) - Abstract
Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
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- 2019
4. Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches
- Author
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Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Oregon Research Institute (ORI), Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Stockholm County Council, Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), University of Split, Azienda Ospedaliera di Padova, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Nutrition-Dietetics, Harokopio University of Athens, University of Athens Medical School [Athens], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Medstar Research Institute, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, National and Kapodistrian University of Athens (NKUA), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Weill Medical College of Cornell University [New York], Department of Genomics, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Tokai University, Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), National Institute for Health and Welfare [Helsinki], Medizinische Universität Wien = Medical University of Vienna, University of California [San Diego] (UC San Diego), University of California, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Computing [Dublin], Dublin City University [Dublin] (DCU), University of Helsinki, University Medical Center [Utrecht], Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC, The M Sklodowska-Curie Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Università degli studi della Campania 'Luigi Vanvitelli', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Queensland Institute of Medical Research, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Estonian Genome and Medicine, University of Tartu, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, Università degli Studi di Salerno (UNISA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Vanderbilt University School of Medicine [Nashville], Charles University [Prague] (CU), Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K, Norwegian Institute of Public Health [Oslo] (NIPH), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institute of Medical Informatics, Biometry and Epidemiology, The Scripps Translational Science Institute and The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Leiden University Medical Center (LUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, The Jackson Laboratory [Bar Harbor] (JAX), The Nofer Institute of Occupational Medicine, Università degli Studi di Perugia (UNIPG), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department Biostatistics University of North Carolina, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Institute of Hygiene and Epidemiology, Charles University and General University Hospital-First Faculty of Medicine, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oslo (UiO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Vall d'Hebron University Hospital [Barcelona], Rheumatology Unit, University of Bergen (UiB), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Masaryk Memorial Cancer Institute (RECAMO), Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Institute of Psychiatry-King‘s College London, Cardiff University-Medical Research Council, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
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Adult ,Male ,Multifactorial Inheritance ,Adolescent ,behavioral disciplines and activities ,Article ,Feeding and Eating Disorders ,Young Adult ,[SCCO]Cognitive science ,Polygenic risk score ,Risk Factors ,mental disorders ,Humans ,ADHD ,Genetic epidemiology ,Registries ,Child ,Sweden ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Eating disorder ,Anorexia nervosa ,Bulimia nervosa ,Eating disorders ,Attention Deficit Disorder with Hyperactivity ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
International audience; BACKGROUND:Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.METHODS:We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).RESULTS:Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.CONCLUSIONS:We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.
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- 2019
5. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
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Symen Ligthart, Ahmad Vaez, Urmo Võsa, Maria G. Stathopoulou, Paul S. de Vries, Bram P. Prins, Peter J. Van der Most, Toshiko Tanaka, Elnaz Naderi, Lynda M. Rose, Ying Wu, Robert Karlsson, Maja Barbalic, Honghuang Lin, René Pool, Gu Zhu, Aurélien Macé, Carlo Sidore, Stella Trompet, Massimo Mangino, Maria Sabater-Lleal, John P. Kemp, Ali Abbasi, Tim Kacprowski, Niek Verweij, Albert V. Smith, Tao Huang, Carola Marzi, Mary F. Feitosa, Kurt K. Lohman, Marcus E. Kleber, Yuri Milaneschi, Christian Mueller, Mahmudul Huq, Efthymia Vlachopoulou, Leo-Pekka Lyytikäinen, Christopher Oldmeadow, Joris Deelen, Markus Perola, Jing Hua Zhao, Bjarke Feenstra, Marzyeh Amini, Jari Lahti, Katharina E. Schraut, Myriam Fornage, Bhoom Suktitipat, Wei-Min Chen, Xiaohui Li, Teresa Nutile, Giovanni Malerba, Jian’an Luan, Tom Bak, Nicholas Schork, Fabiola Del Greco M., Elisabeth Thiering, Anubha Mahajan, Riccardo E. Marioni, Evelin Mihailov, Joel Eriksson, Ayse Bilge Ozel, Weihua Zhang, Maria Nethander, Yu-Ching Cheng, Stella Aslibekyan, Wei Ang, Ilaria Gandin, Loïc Yengo, Laura Portas, Charles Kooperberg, Edith Hofer, Kumar B. Rajan, Claudia Schurmann, Wouter den Hollander, Tarunveer S. Ahluwalia, Jing Zhao, Harmen H.M. Draisma, Ian Ford, Nicholas Timpson, Alexander Teumer, Hongyan Huang, Simone Wahl, YongMei Liu, Jie Huang, Hae-Won Uh, Frank Geller, Peter K. Joshi, Lisa R. Yanek, Elisabetta Trabetti, Benjamin Lehne, Diego Vozzi, Marie Verbanck, Ginevra Biino, Yasaman Saba, Ingrid Meulenbelt, Jeff R. O’Connell, Markku Laakso, Franco Giulianini, Patrik K.E. Magnusson, Christie M. Ballantyne, Jouke Jan Hottenga, Grant W. Montgomery, Fernando Rivadineira, Rico Rueedi, Maristella Steri, Karl-Heinz Herzig, David J. Stott, Cristina Menni, Mattias Frånberg, Beate St. Pourcain, Stephan B. Felix, Tune H. Pers, Stephan J.L. Bakker, Peter Kraft, Annette Peters, Dhananjay Vaidya, Graciela Delgado, Johannes H. Smit, Vera Großmann, Juha Sinisalo, Ilkka Seppälä, Stephen R. Williams, Elizabeth G. Holliday, Matthijs Moed, Claudia Langenberg, Katri Räikkönen, Jingzhong Ding, Harry Campbell, Michele M. Sale, Yii-Der I. Chen, Alan L. James, Daniela Ruggiero, Nicole Soranzo, Catharina A. Hartman, Erin N. Smith, Gerald S. Berenson, Christian Fuchsberger, Dena Hernandez, Carla M.T. Tiesler, Vilmantas Giedraitis, David Liewald, Krista Fischer, Dan Mellström, Anders Larsson, Yunmei Wang, William R. Scott, Matthias Lorentzon, John Beilby, Kathleen A. Ryan, Craig E. Pennell, Dragana Vuckovic, Beverly Balkau, Maria Pina Concas, Reinhold Schmidt, Carlos F. Mendes de Leon, Erwin P. Bottinger, Margreet Kloppenburg, Lavinia Paternoster, Michael Boehnke, A.W. Musk, Gonneke Willemsen, David M. Evans, Pamela A.F. Madden, Mika Kähönen, Zoltán Kutalik, Magdalena Zoledziewska, Ville Karhunen, Stephen B. Kritchevsky, Naveed Sattar, Genevieve Lachance, Robert Clarke, Tamara B. Harris, Olli T. Raitakari, John R. Attia, Diana van Heemst, Eero Kajantie, Rossella Sorice, Giovanni Gambaro, Robert A. Scott, Andrew A. Hicks, Luigi Ferrucci, Marie Standl, Cecilia M. Lindgren, John M. Starr, Magnus Karlsson, Lars Lind, Jun Z. Li, John C. Chambers, Trevor A. Mori, Eco J.C.N. de Geus, Andrew C. Heath, Nicholas G. Martin, Juha Auvinen, Brendan M. Buckley, Anton J.M. de Craen, Melanie Waldenberger, Konstantin Strauch, Thomas Meitinger, Rodney J. Scott, Mark McEvoy, Marian Beekman, Cristina Bombieri, Paul M. Ridker, Karen L. Mohlke, Nancy L. Pedersen, Alanna C. Morrison, Dorret I. Boomsma, John B. Whitfield, David P. Strachan, Albert Hofman, Peter Vollenweider, Francesco Cucca, Marjo-Riitta Jarvelin, J. Wouter Jukema, Tim D. Spector, Anders Hamsten, Tanja Zeller, André G. Uitterlinden, Matthias Nauck, Vilmundur Gudnason, Lu Qi, Harald Grallert, Ingrid B. Borecki, Jerome I. Rotter, Winfried März, Philipp S. Wild, Marja-Liisa Lokki, Michael Boyle, Veikko Salomaa, Mads Melbye, Johan G. Eriksson, James F. Wilson, Brenda W.J.H. Penninx, Diane M. Becker, Bradford B. Worrall, Greg Gibson, Ronald M. Krauss, Marina Ciullo, Gianluigi Zaza, Nicholas J. Wareham, Albertine J. Oldehinkel, Lyle J. Palmer, Sarah S. Murray, Peter P. Pramstaller, Stefania Bandinelli, Joachim Heinrich, Erik Ingelsson, Ian J. Deary, Reedik Mägi, Liesbeth Vandenput, Pim van der Harst, Karl C. Desch, Jaspal S. Kooner, Claes Ohlsson, Caroline Hayward, Terho Lehtimäki, Alan R. Shuldiner, Donna K. Arnett, Lawrence J. Beilin, Antonietta Robino, Philippe Froguel, Mario Pirastu, Tine Jess, Wolfgang Koenig, Ruth J.F. Loos, Denis A. Evans, Helena Schmidt, George Davey Smith, P. Eline Slagboom, Gudny Eiriksdottir, Andrew P. Morris, Bruce M. Psaty, Russell P. Tracy, Ilja M. Nolte, Eric Boerwinkle, Sophie Visvikis-Siest, Alex P. Reiner, Myron Gross, Joshua C. Bis, Lude Franke, Oscar H. Franco, Emelia J. Benjamin, Daniel I. Chasman, Josée Dupuis, Harold Snieder, Abbas Dehghan, Behrooz Z. Alizadeh, H. Marike Boezen, Gerjan Navis, Marianne Rots, Morris Swertz, Bruce H.R. Wolffenbuttel, Cisca Wijmenga, Emelia Benjamin, Tarunveer Singh Ahluwalia, James Meigs, Russell Tracy, Josh Bis, Nathan Pankratz, Alex Rainer, James G. Wilson, Josee Dupuis, Bram Prins, Urmo Vaso, Maria Stathopoulou, Terho Lehtimaki, Yalda Jamshidi, Sophie Siest, Andre G. Uitterlinden, Mohammadreza Abdollahi, Renate Schnabel, Ursula M. Schick, Aldi Kraja, Yi-Hsiang Hsu, Daniel S. Tylee, Alyson Zwicker, Rudolf Uher, George Davey-Smith, Andrew Hicks, Cornelia M. van Duijn, Cavin Ward-Caviness, J. Rotter, Ken Rice, Leslie Lange, Eco de Geus, Kari Matti Makela, David Stacey, Johan Eriksson, Tim M. Frayling, Eline P. Slagboom, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University Medical Center Groningen [Groningen] (UMCG), University of Isfahan, University of Tartu, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The University of Texas Health Science Center at Houston (UTHealth), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Split, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Process & Energy Laboratory, Delft University of Technology (TU Delft), Grand Lyon : communauté urbaine de Lyon, Interuniversity Cardiology Institute Netherlands, Department of Twin Research and Genetic Epidemiology, King's College London, London, Huazhong University of Science and Technology [Wuhan] (HUST), Division of Statistical Genomics, Washington University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Institut fuer Theoretische Physik (Institut fuer Theoretische Physik), Universität Heidelberg [Heidelberg] = Heidelberg University, Molecular Epidemiology, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Mahidol University [Bangkok], Northwest A and F University, Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biophysics, CNR, Naples, Università degli studi di Verona = University of Verona (UNIVR), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], University of Maryland School of Medicine, University of Maryland System, Institut National de l'Environnement Industriel et des Risques (INERIS), Institute of Pop. Genetics, CNR, Sassari, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, IT University of Copenhagen (ITU), Robertson Centre for Biostatistics, University of Glasgow, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, King‘s College London, Jinan University [Guangzhou], Institute of Oceanology [China], School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Shardna life science Pula Cagliari, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Medstar Research Institute, Department of Cardiology, Ernst-Moritz-Arndt University, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Department of Internal Medicine, University of Groningen and University Medical Center Groningen, Department of Epidemiology, Harvard School of Public Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Metacohorts Consortium, INEOS Technologies (SWITZERLAND), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, University of Edinburgh, School of Population Health [Crawley, Western Australia], The University of Western Australia (UWA), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), The Scripps Translational Science Institute and Scripps Health, Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, Centre for Population Health Sciences, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Luleå University of Technology (LUT), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Austrian Institute of Technology [Vienna] (AIT), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), Department of Rheumatology and Clinical Epidemiology [Leiden University Medical Center] (LUMC), Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden-Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Virginia, Tampere University Hospital, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Department of Pathological Biochemistry, Royal Infirmary, Oxford University, University of Oxford, University of Newcastle [Callaghan, Australia] (UoN), Department of neurology, Institute of Metabolic Science, MRC, The Wellcome Trust Centre for Human Genetics [Oxford], Uppsala Universitet [Uppsala], QIMR Berghofer Medical Research Institute, Institute of Genetic Epidemiology [Neuherberg, Germany], Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Schizophrenia Research Institute [Sydney], Department of Genetics, University of North Carolina System (UNC)-University of North Carolina System (UNC), Vrije Universiteit Brussel (VUB), Population Health Sciences and Education, St George's University of London, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Health Sciences and Biocenter Oulu, University of Oulu, Medizinische Klinik und Poliklinik, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institute of Clinical Chemistry and Laboratory Medicine, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Departments of Epidemiology and Nutrition, Institute of Epidemiology [Neuherberg] (EPI), Medical University Graz, Transplantation Laboratory [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], CLinical Psychology, Genetics and Pathology, Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Center For Narcolepsy, Stanford University, Centre for Bone and Arthritis Research, University of Gothenburg (GU)-Institute of Medicine, MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh, University of Maryland School of Medicine [Baltimore, MD, USA], Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Stockholm], Stockholm University, University of Bristol [Bristol], Universiteit Leiden, Department of Epidemiology, University of Washington, University of Washington [Seattle], Department of Epidemiology [Rotterdam], University of Groningen [Groningen], Dutch Initiative on Crohn and Colitis (ICC), Icelandic Heart Association [Kopavogur, Iceland] (IHA), Department of Physiology and Biophysics [Jackson, MS, USA], University of Southern Mississippi (USM), Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Department of Social Medicine, School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Medicine [Aurora, CO, USA], University of Colorado [Denver], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Mathematical Institute [Oxford] (MI), Institute of Psychiatry, Psychology & Neuroscience, King's College London, LifeLines Cohort Study, CHARGE Inflammation Working Group, Ligthart, S., Vaez, A., Vosa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., Van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., Wu, Y., Karlsson, R., Barbalic, M., Lin, H., Pool, R., Zhu, G., Mace, A., Sidore, C., Trompet, S., Mangino, M., Sabater-Lleal, M., Kemp, J. P., Abbasi, A., Kacprowski, T., Verweij, N., Smith, A. V., Huang, T., Marzi, C., Feitosa, M. F., Lohman, K. K., Kleber, M. E., Milaneschi, Y., Mueller, C., Huq, M., Vlachopoulou, E., Lyytikainen, L. -P., Oldmeadow, C., Deelen, J., Perola, M., Zhao, J. H., Feenstra, B., Alizadeh, B. Z., Boezen, H. M., Franke, L., van der Harst, P., Navis, G., Rots, M., Snieder, H., Swertz, M., Wolffenbuttel, B. H. R., Wijmenga, C., Amini, M., Benjamin, E., Chasman, D. I., Dehghan, A., Ahluwalia, T. S., Meigs, J., Tracy, R., Bis, J., Eiriksdottir, G., Pankratz, N., Gross, M., Rainer, A., Wilson, J. G., Psaty, B. M., Dupuis, J., Prins, B., Vaso, U., Stathopoulou, M., Lehtimaki, T., Koenig, W., Jamshidi, Y., Siest, S., Uitterlinden, A. G., Abdollahi, M., Schnabel, R., Schick, U. M., Nolte, I. M., Kraja, A., Hsu, Y. -H., Tylee, D. S., Zwicker, A., Uher, R., Davey-Smith, G., Morrison, A. C., Hicks, A., van Duijn, C. M., Ward-Caviness, C., Boerwinkle, E., Rotter, J., Rice, K., Lange, L., de Geus, E., Morris, A. P., Makela, K. M., Stacey, D., Eriksson, J., Frayling, T. M., Slagboom, E. P., Lahti, J., Schraut, K. E., Fornage, M., Suktitipat, B., Chen, W. -M., Li, X., Nutile, T., Malerba, G., Luan, J., Bak, T., Schork, N., Del Greco, M. F., Thiering, E., Mahajan, A., Marioni, R. E., Mihailov, E., Ozel, A. B., Zhang, W., Nethander, M., Cheng, Y. -C., Aslibekyan, S., Ang, W., Gandin, I., Yengo, L., Portas, L., Kooperberg, C., Hofer, E., Rajan, K. B., Schurmann, C., den Hollander, W., Zhao, J., Draisma, H. H. M., Ford, I., Timpson, N., Teumer, A., Huang, H., Wahl, S., Liu, Y., Huang, J., Uh, H. -W., Geller, F., Joshi, P. K., Yanek, L. R., Trabetti, E., Lehne, B., Vozzi, D., Verbanck, M., Biino, G., Saba, Y., Meulenbelt, I., O'Connell, J. R., Laakso, M., Giulianini, F., Magnusson, P. K. E., Ballantyne, C. M., Hottenga, J. J., Montgomery, G. W., Rivadineira, F., Rueedi, R., Steri, M., Herzig, K. -H., Stott, D. J., Menni, C., Franberg, M., S, t. Pourcain B., Felix, S. B., Pers, T. H., Bakker, S. J. L., Kraft, P., Peters, A., Vaidya, D., Delgado, G., Smit, J. H., Grossmann, V., Sinisalo, J., Seppala, I., Williams, S. R., Holliday, E. G., Moed, M., Langenberg, C., Raikkonen, K., Ding, J., Campbell, H., Sale, M. M., Chen, Y. -D. I., James, A. L., Ruggiero, D., Soranzo, N., Hartman, C. A., Smith, E. N., Berenson, G. S., Fuchsberger, C., Hernandez, D., Tiesler, C. M. T., Giedraitis, V., Liewald, D., Fischer, K., Mellstrom, D., Larsson, A., Wang, Y., Scott, W. R., Lorentzon, M., Beilby, J., Ryan, K. A., Pennell, C. E., Vuckovic, D., Balkau, B., Concas, M. P., Schmidt, R., Mendes de Leon, C. F., Bottinger, E. P., Kloppenburg, M., Paternoster, L., Boehnke, M., Musk, A. W., Willemsen, G., Evans, D. M., Madden, P. A. F., Kahonen, M., Kutalik, Z., Zoledziewska, M., Karhunen, V., Kritchevsky, S. B., Sattar, N., Lachance, G., Clarke, R., Harris, T. B., Raitakari, O. T., Attia, J. R., van Heemst, D., Kajantie, E., Sorice, R., Gambaro, G., Scott, R. A., Hicks, A. A., Ferrucci, L., Standl, M., Lindgren, C. M., Starr, J. M., Karlsson, M., Lind, L., Li, J. Z., Chambers, J. C., Mori, T. A., de Geus, E. J. C. N., Heath, A. C., Martin, N. G., Auvinen, J., Buckley, B. M., de Craen, A. J. M., Waldenberger, M., Strauch, K., Meitinger, T., Scott, R. J., Mcevoy, M., Beekman, M., Bombieri, C., Ridker, P. M., Mohlke, K. L., Pedersen, N. L., Boomsma, D. I., Whitfield, J. B., Strachan, D. P., Hofman, A., Vollenweider, P., Cucca, F., Jarvelin, M. -R., Jukema, J. W., Spector, T. D., Hamsten, A., Zeller, T., Nauck, M., Gudnason, V., Qi, L., Grallert, H., Borecki, I. B., Rotter, J. I., Marz, W., Wild, P. S., Lokki, M. -L., Boyle, M., Salomaa, V., Melbye, M., Eriksson, J. G., Wilson, J. F., Penninx, B. W. J. H., Becker, D. M., Worrall, B. B., Gibson, G., Krauss, R. M., Ciullo, M., Zaza, G., Wareham, N. J., Oldehinkel, A. J., Palmer, L. J., Murray, S. S., Pramstaller, P. P., Bandinelli, S., Heinrich, J., Ingelsson, E., Deary, I. J., Magi, R., Vandenput, L., Desch, K. C., Kooner, J. S., Ohlsson, C., Hayward, C., Shuldiner, A. R., Arnett, D. K., Beilin, L. J., Robino, A., Froguel, P., Pirastu, M., Jess, T., Loos, R. J. F., Evans, D. A., Schmidt, H., Slagboom, P. E., Tracy, R. P., Visvikis-Siest, S., Reiner, A. P., Bis, J. C., Franco, O. H., Benjamin, E. J., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Epidemiology, Internal Medicine, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), VU University medical center, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Universität Heidelberg [Heidelberg], University of Verona (UNIVR), Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IT University of Copenhagen, Technical University of Denmark [Lyngby] (DTU), Consiglio Nazionale delle Ricerche (CNR), University of Virginia [Charlottesville], Université de Lausanne (UNIL), University of Oxford [Oxford], University of Newcastle [Australia] (UoN), Centre d'économie industrielle i3 (CERNA i3), Centre National de la Recherche Scientifique (CNRS)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Helmholtz-Zentrum München (HZM), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Universitätsmedizin der Johannes-Gutenberg Universität Mainz, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Cardiff University-Medical Research Council, University of California-University of California, and DE CARVALHO, Philippe
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0301 basic medicine ,Male ,Netherlands Twin Register (NTR) ,Bipolar Disorder ,LD SCORE REGRESSION ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Body Mass Index ,inflammatory disorder ,80 and over ,WIDE ASSOCIATION ,EPIDEMIOLOGY ,ta318 ,International HapMap Project ,Child ,Genetics (clinical) ,2. Zero hunger ,Genetics ,Genetics & Heredity ,Aged, 80 and over ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,C-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biology ,system biology ,DEPICT ,Mendelian Randomization Analysis ,11 Medical And Health Sciences ,Middle Aged ,C-reactive protein ,coronary artery disease ,genome-wide association study ,inflammation ,inflammatory disorders ,Mendelian randomization ,schizophrenia ,Adolescent ,Adult ,Aged ,Biomarkers ,C-Reactive Protein ,Female ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Inflammation ,Liver ,Metabolic Networks and Pathways ,Schizophrenia ,Young Adult ,3. Good health ,[SDV] Life Sciences [q-bio] ,Medical genetics ,Biomarker (medicine) ,Life Sciences & Biomedicine ,Human ,medicine.medical_specialty ,CHARGE Inflammation Working Group ,Biology ,IMMUNITY ,ta3111 ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,CORONARY-HEART-DISEASE ,Mendelian Randomization Analysi ,1000 Genomes Project ,METAANALYSIS ,Genetic association ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Science & Technology ,ta1184 ,Metabolic Networks and Pathway ,Biomarker ,INSTRUMENTS ,06 Biological Sciences ,030104 developmental biology ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,LifeLines Cohort Study - Abstract
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
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- 2018
6. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants
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Yiallouros, Panayiotis K., Escobedo-de la Peña, Jorge, Zhou, Bin, Bentham, James, Di Cesare, Mariachiara, Bixby, Honor, Danaei, Goodarz, Hajifathalian, Kaveh, Taddei, Cristina, Carrillo-Larco, Rodrigo M., Djalalinia, Shirin, Khatibzadeh, Shahab, Lugero, Charles, Peykari, Niloofar, Zhang, Wan Zhu, Bennett, James, Bilano, Ver, Stevens, Gretchen A., Cowan, Melanie J., Riley, Leanne M., Chen, Zhengming, Hambleton, Ian R., Jackson, Rod T., Kengne, Andre Pascal, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Malekzadeh, Reza, Neuhauser, Hannelore K., Sorić, Maroje, Starc, Gregor, Sundström, Johan, Woodward, Mark, Ezzati, Majid, Abarca-Gómez, Leandra, Abdeen, Ziad A., Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadvand, Alireza, Ahrens, Wolfgang, Ajlouni, Kamel, Akhtaeva, Nazgul, Al-Raddadi, Rajaa, Ali, Mohamed M., Ali, Osman, Alkerwi, Ala'a, Aly, Eman, Amarapurkar, Deepak N., Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Ängquist, Lars H., Anjana, Ranjit Mohan, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assunção, Maria Cecília F., Avdicová, Mária, Azevedo, Ana, Azizi, Fereidoun, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R., Barbagallo, Carlo M., Barceló, Alberto, Barkat, Amina, Barros, Aluisio J. 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B(as), Bugge, Anna, Burns, Con, Bursztyn, Michael, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cameron, Christine, Can, Günay, Cândido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Cheng, Ching-Yu, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, María-Dolores, Cho, Belong, Cho, Yumi, Christofaro, Diego G., Chudek, Jerzy, Cifkova, Renata, Cinteza, Eliza, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., Cruz, Juan J., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Smedt, Delphine, Deepa, Mohan, Dehghan, Abbas, Delisle, Hélène, Deschamps, Valérie, Dhana, Klodian, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Do, Ha T. 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Donfrancesco, Chiara, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Doua, Kouamelan, Drygas, Wojciech, Dulskiene, Virginija, Džakula, Aleksandar, Dzerve, Vilni, Dziankowska-Zaborszczyk, Elzbieta, Eggertsen, Robert, Ekelund, Ulf, El Ati, Jalila, Elliott, Paul, Elosua, Roberto, Erasmus, Rajiv T, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, Escobedo-de la Peña, Jorge, Evans, Alun, Faeh, David, Fall, Caroline H, Farzadfar, Farshad, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D, Fischer, Krista, Föger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Forsner, Maria, Fouad, Heba M, Francis, Damian K, do Carmo Franco, Maria, Franco, Oscar H, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Galvano, Fabio, Garcia-de-la-Hera, Manoli, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M, Ghasemian, Anoosheh, Ghimire, Anup, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Goldsmith, Rebecca A, Gonçalves, Helen, Gonzalez-Gross, Marcela, González-Rivas, Juan P, Gorbea, Mariano Bonet, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, Grøntved, Ander, Grosso, Giuseppe, Gruden, Gabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idri, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Hadaegh, Farzad, Halkjær, Jytte, Hardy, Rebecca, Hari Kumar, Rachakulla, Hata, Jun, Hayes, Alison J, He, Jiang, He, Yuna, Elisabeth, Marleen, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Hofman, Albert, Dinc, Gonul Horasan, Horimoto, Andrea R V R, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Than Htike, Maung Maung, Hu, Yonghua, Huerta, José María, Huisman, Martijn, Husseini, Abdullatif S, Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G, Ibrahim, Mohsen M, Wong, Norazizah Ibrahim, Ikeda, Nayu, Ikram, M Arfan, Irazola, Vilma E, Islam, Muhammad, al-Safi Ismail, Aziz, Ivkovic, Vanja, Iwasaki, Masanori, Jacobs, Jeremy M, Jaddou, Hashem, Jafar, Tazeen, Jamrozik, Konrad, Janszky, Imre, Jasienska, Grazyna, Jelaković, Ana, Jelaković, Bojan, Jennings, Garry, Jeong, Seung-lyeal, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattia, Jokelainen, Jari J, Jonas, Jost B, Jørgensen, Torben, Joshi, Pradeep, Jóźwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Jureša, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O, Kalter-Leibovici, Ofra, Kamaruddin, Nor Azmi, Karki, Khem B, Kasaeian, Amir, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C G, Kengne, Andre P, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khateeb, Mohammad, Khaw, Kay-Tee, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kim, Yeon-Yong, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kuh, Diana, Kujala, Urho M, Kulaga, Zbigniew, Krishna Kumar, R, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Laugsand, Lars E, Le Nguyen Bao, Khanh, Le, Tuyen D, Leclercq, Catherine, Lee, Jeannette, Lee, Jeonghee, Lehtimäki, Terho, León-Muñoz, Luz M, Levitt, Naomi S, Li, Yanping, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lind, Lar, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lorbeer, Roberto, Lotufo, Paulo A, Lozano, José Eugenio, Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L L, Machi, Suka, Maggi, Stefania, Magliano, Dianna J, Magriplis, Emmanuella, Majer, Marjeta, Makdisse, Marcia, Malhotra, Rahul, Mallikharjuna Rao, Kodavanti, Malyutina, Sofia, Manios, Yanni, Mann, Jim I, Manzato, Enzo, Margozzini, Paula, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mathiesen, Ellisiv B, Matijasevich, Alicia, Matsha, Tandi E, Mbanya, Jean Claude N, Mc Donald Posso, Anselmo J, McFarlane, Shelly R, McGarvey, Stephen T, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Mediene-Benchekor, Sounnia, Medzioniene, Jurate, Meirhaeghe, Aline, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Mikkel, Kairit, Miller, Jody C, Minderico, Cláudia S, Francisco, Juan, Miranda, J Jaime, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Modesti, Pietro A, Mohamed, Mostafa K, Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Mohanna, Salim, Mohd Yusoff, Muhammad Fadhli, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota, Jorge, Esmaeel Motlagh, Mohammad, Motta, Jorge, Msyamboza, Kelias P, Mu, Thet Thet, Muiesan, Maria L, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musil, Vera, Nabipour, Iraj, Nagel, Gabriele, Naidu, Balkish M, Nakamura, Harunobu, Námešná, Jana, Nang, Ei Ei K, Nangia, Vinay B, Narake, Sameer, Nauck, Matthia, Navarrete-Muñoz, Eva Maria, Ndiaye, Ndeye Coumba, Neal, William A, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nguyen, Quang V, Nieto-Martínez, Ramfis E, Niiranen, Teemu J, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Noorbala, Ahmad Ali, Norat, Teresa, Noto, Davide, Al Nsour, Mohannad, O'Reilly, Dermot, Oda, Eiji, Oehlers, Glenn, Oh, Kyungwon, Ohara, Kumiko, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Parnell, Winsome R, Parsaeian, Mahboubeh, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Peeters, Petra H, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Pham, Son Thai, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Plans-Rubió, Pedro, Polašek, Ozren, Porta, Miquel, Portegies, Marileen L P, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F, Puder, Jardena J, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Ramachandra Rao, Sudha, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A, Redon, Josep, Reganit, Paul Ferdinand M, Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Rinke de Wit, Tobias F, Ritti-Dias, Raphael M, Robinson, Sian M, Robitaille, Cynthia, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Rojas-Martinez, Rosalba, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Roy, Joel G R, Rubinstein, Adolfo, Sandra Ruiz-Betancourt, Blanca, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S, Saidi, Olfa, Sakarya, Sibel, Salanave, Benoit, Salazar Martinez, Eduardo, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Sánchez-Abanto, Jose, Sans, Susana, Santos, Diana A, Santos, Ina S, Nunes dos Santos, Renata, Santos, Rute, Saramies, Jouko L, Sardinha, Luis B, Sarganas, Giselle, Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savva, Scazufca, Marcia, Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O, Schöttker, Ben, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sharma, Sanjib K, Shaw, Jonathan E, Shibuya, Kenji, Shin, Dong Wook, Shin, Youchan, Si-Ramlee, Khairil, Siantar, Rosalynn, Sibai, Abla M, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöström, Michael, Skovbjerg, Sine, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C, Snijder, Marieke B, So, Hung-Kwan, Sobngwi, Eugène, Söderberg, Stefan, Solfrizzi, Vincenzo, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild I A, Soric, Maroje, Jérome, Charles Sossa, Soumare, Aicha, Staessen, Jan A, Stathopoulou, Maria G, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G, Shyong Tai, E, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B, Tautu, Oana-Florentina, Taylor, Anne, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thuesen, Betina H, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Tormo, María José, Torrent, Matie, Traissac, Pierre, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh T H, Trivedi, Atul, Tshepo, Lechaba, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice E, Ulmer, Hanno, Uusitalo, Hannu M T, Valdivia, Gonzalo, Valvi, Damaskini, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, van Rossem, Lenie, Van Schoor, Natasja M, van Valkengoed, Irene G M, Vanderschueren, Dirk, Vanuzzo, Diego, Vatten, Lar, Vega, Toma, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Monique Verschuren, W M, Verstraeten, Roosmarijn, Victora, Cesar G, Viet, Lucie, Viikari-Juntura, Eira, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Sari, Wade, Alisha N, Wagner, Aline, Walton, Janette, Wan Bebakar, Wan Mohamad, Wan Mohamud, Wan Nazaimoon, Wanderley, Rildo S, Wang, Ming-Dong, Wang, Qian, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Wedderkopp, Niel, Weerasekera, Deepa, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wijga, Alet H, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Emmanuel A, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Justin Y Y, Wong, Tien Yin, Woo, Jean, Giwercman Wu, Aleksander, Wu, Frederick C, Wu, Shouling, Xu, Haiquan, Yan, Weili, Yang, Xiaoguang, Ye, Xingwang, Yiallouros, Panayiotis K, Yoshihara, Akihiro, Younger-Coleman, Novie O, Yusoff, Ahmad Faudzi, Zainuddin, Ahmad Ali, Zambon, Sabina, Zampelas, Antoni, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Wei, Zheng, Yingfeng, Zhu, Dan, Zhussupov, Baurzhan, Zimmermann, Esther, Cisneros, Julio Zuñiga, The State Key Laboratory of Cell Biology [Shanghai, China] (CAS Center for Excellence in Molecular Cell Science), Shanghai Institute of Biochemistry and Cell Biology [Shanghai, China]-University of Chinese Academy of Sciences [Shanghai, China], Imperial College London, University of Kentucky, Middlesex University, Cleveland Clinic, Universidad Peruana Cayetano Heredia (UPCH), Brandeis University, Mulago Hospital [Kampala, Ouganda], Department of Epidemiology and Public Health, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), World Health Organisation (WHO), Al-Quds University, Discipline of Medicine, University of South Australia [Adelaide], Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, Centre for Industrial Management, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Preventive Medicine, Copenhagen University Hospitals, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Dept. Atherosclerose, University of Iceland [Reykjavik], Institute for Biotechnology and Bioengineering (IBB), Technical University of Lisbon, Medical University of Łódź (MUL), Department of Preventive Medicine and Public Health, Universidad Autónoma de Madrid (UAM), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM), Sunder Lal Jain Hospital, Ufa Eye Research Institute [Bashkortostan], National Institute of Public Health, Department of Epidemiology, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association-Leibniz Association, CHU Toulouse [Toulouse], Institute of Social and Preventive Medicine, Lausanne university hospital, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Medical Sciences [Turin, Italy] (DMS), Università degli studi di Torino = University of Turin (UNITO), ASU - School for Engineering of Matter, Transport and Energy, Arizona State University [Tempe] (ASU), Universidade do Porto = University of Porto, University of Oxford [Oxford], Cancer & Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), 2nd Department of Internal Medicine, Molecular Medicine, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-IRC KULAK, Department of Public Health, State University of Ghent, MRC Lifecourse Epidemiology Unit [Southampton, UK], University of Southampton, Réseau International des Instituts Pasteur (RIIP), Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Sahlgrenska University Hospital [Gothenburg], Institute of Metabolic Science, MRC, Institut National de Nutrition et de Technologie Alimentaire (INNTA), University of Huddersfield, IMIM-Hospital del Mar, Generalitat de Catalunya, Medstar Research Institute, Queen's University [Belfast] (QUB), Medical Research Council, Applied Sciences, National Research Institute on Food and Nutrition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Innsbruck Medical University [Austria] (IMU), Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Laboratoire d'Etude des Mammifères Marins (LEMM), Océanopolis [Brest], Faculté de Médecine Henri Warembourg - Université de Lille, Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark (SDU), Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Centro Investig Quim Aplicada, Coahuila, Mexico, Centro Investigacion en Quimica Aplicada, Coahuila, Mexico, University of Geneva [Switzerland], Department of Civil Engineering [Hamirpur], National Institute of Technology [Hamirpur], Health Services Research Unit, Danish Cancer Society, Institute of Cancer Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), University College of London [London] (UCL), The Georges Institute for International Health, The University of Sydney, School of Information Technology, Deakin University Waurn Ponds, Faculté de Médecine, Université Djilali Liabès [Sidi-Bel-Abbès], Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), VU University Medical Center [Amsterdam], Universiteit Gent = Ghent University [Belgium] (UGENT), Faculty of Agricultural and Food Science, American University of Beirut [Beyrouth] (AUB), Åbo Akademi University [Turku], Department of Public Health Sciences, Karolinska Institutet [Stockholm], Great Lakes Institute for Environmental Research, University of Windsor [Ca], Universität Heidelberg [Heidelberg], Research Center for Prevention and Health, University of Ljubljana, Division of Cancer Epidemiology, University of Crete School of medicine, School of Public Health and Clinical Nutrition, University of Eastern Finland, Institute of Epidemiology and Social Medicine, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Research Institute of Child Nutrition Dortmund, Rheinische Friedrich-Wilhelms-Universität Bonn, Cancer Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Oncology, University of Tampere Medical School, University of Tampere, Wageningen University and Research [Wageningen] (WUR), Centre for Environmental Health, National Institue of Public Health, School of Public Health, The University of Hong Kong (HKU), Tehran University of Medical Sciences, Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN), INRAN, National University of Singapore (NUS), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Uppsala Universitet [Uppsala], Department of Public Health and Community Medicine, University of Gothenburg (GU), Institute of Earthquake Science, CEA, Beijing, CEA, Beijing, University of Porto Medical School, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aging Program, National research council, Padua, Italy, Baker IDI Heart and Diabetes Institute, Institute of Internal Medicine, Russian Academy of Medical Sciences, Department of Nutrition and Dietetics, Harokopio University, Emory University [Atlanta, GA], Départment of Biotechnology, Faculty of Science, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Institut National de la Santé et de la Recherche Médicale (INSERM), University of Tartu, Department of Community, Université Ain Shams-Faculty of Medicine-Environmental and Occupational Medicine, Pécsi Tudemányegyetem, Department of Community, Environmental and Occupational Medicine, Université Ain Shams, Research Centre in Physical Activity, Health and Leisure, Nutrition and Metabolism Section, International Agency for Research on Cancer, Bushehr University of Medical Sciences, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Università degli studi di Palermo - University of Palermo, MRc Environmental Epidemiology Unit, Department of Cardiology and Department of Clinical Epidemiology, Aarhus University Hospital, Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Department of Epidemiology and Population Studies, Jagiellonian University, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Social Robotics Laboratory, University of Freiburg, Freiburg im Breisgau, Department of Ophthalmology, Universitätsklinikum Mannheim, Medizinische Fakultät Mannheim der Universität Heidelberg, University of Bari Aldo Moro (UNIBA), Department of Cardiology, Eastbourne General Hospital, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), King‘s College London, Public Health Sciences, University of Edinburgh, Movement Disorders and Tourette Centre, Genetica medicala, Victor Babeş University of Medicine and Pharmacy (UMFT), Andrology Unit, United Laboratories of Tartu University Clinics, Tampere University Hospital, Department of Hygiene and Epidemiology, Dept of Epidemiology and Public Health, Department of Epidemiology and Biostatistics, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Emergency and Cardiovascular Medicine, Sahlgrenska Academy, Institut de Veille Sanitaire (INVS), Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain, parent, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], University of São Paulo (USP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institute for plasma research, Institute for Plasma Research, Department of Biosciences and Nutrition, Department of Reproductive Endocrinology, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC - Academic medical center, Central Hospital and Faculty of medicine and biomedical sciences university, University of Yaoundé [Cameroun], Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, School of Computing [Leeds], University of Leeds, Copenhagen University Hospital, Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Applied Food Science, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, University of Amsterdam, Dept. of Social Medecine, Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University Hospital, Africa Centre for Health and Population Studies, University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-Medical Research Council of South Africa, Center for Family and Community Medicine, Department of Neurobiology, Care Sciences and Society, Department of Cardiovascular Sciences [Leuven], Cancer Epidemiology Institute, Department of Epidemiology and Health Promotion (MONICA Data Centre), National Public Health Institute, Nutrition et Alimentation des Populations aux Suds (NutriPass), Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Havard School of Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], University of Kuopio, Tampere University, University Medical Centre Utrecht, Department of Social Medicine, Amsterdam, Center for Metabolic Bone Diseases, Catholic University of Leuven, Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Universidad Miguel Hernández [Elche] (UMH), Institute of Public Health and Clinical Nutrition [Kuopio, Finland], Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Division of Community Health Sciences, St George's University of London, Medizinische Universität Wien = Medical University of Vienna, Medical University of Silesia (SUM), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Innsbruck, National Institute of Hygiene Warsaw, Johns Hopkins University School of Medicine [Baltimore], Food Science and Technology, Beijing Forestry University, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics (CAE-NUAA), NUAA, Chinese Center for Disease Control and Prevention, Department of Applied Mathematics, School of Science, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, Siemens Corporate Research, Siemens AG [Munich], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), This work was supported by the Wellcome Trust [101506/Z/13/Z]., NCD Risk Factor Collaboration (NCD-RisC). We thank WHO country and regional offices and the World Heart Federation for support in data identification and access., Universidad Autonoma de Madrid (UAM), University of Turin, Universidade do Porto, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Lille 2 - Faculté de Médecine, Westfälische Wilhelms-Universität Münster (WWU), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of KwaZulu-Natal (UKZN)-Medical Research Council of South Africa, Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Lund University Diabetes Centre-Lund University [Lund], Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Medical University of Silesia, Katowice, Apollo - University of Cambridge Repository, University of Kentucky (UK), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lausanne University Hospital, University of Oxford, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Université de Genève = University of Geneva (UNIGE), Deakin University [Waurn Ponds], Universiteit Gent = Ghent University (UGENT), Universität Heidelberg [Heidelberg] = Heidelberg University, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Universidade de São Paulo = University of São Paulo (USP), Lund University [Lund], Laboratoire Chrono-environnement (UMR 6249) (LCE), Leopold Franzens Universität Innsbruck - University of Innsbruck, National Institute of Public Health - National Institute of Hygiene [Poland], Yiallouros, Panayiotis K. [0000-0002-8339-9285], Giampaoli, Simona [0000-0002-6679-1488], Moschonis, George [0000-0003-3009-6675], Papandreou, Dimitrios [0000-0002-4923-484X], Stathopoulou, Maria G. [0000-0003-4376-2083], Stergiou, George S. [0000-0002-6132-0038], Trichopoulou, Antonia [0000-0002-7204-6396], Valvi, Damaskini [0000-0003-4633-229X], Chen, Z, Woodward, M, Key, T, and Smith, M
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systolic blood pressure ,Settore MED/09 - Medicina Interna ,blood pressure measurement ,HEALTH EXAMINATION SURVEYS ,Blood Pressure ,Hypertension ,Population Health ,Global Health ,Non-communicable Disease ,Epidemiology ,[SDV]Life Sciences [q-bio] ,global health ,South Asia ,purl.org/pe-repo/ocde/ford#3.03.09 [https] ,kohonnut verenpaine ,Medicine and Health Sciences ,middle income country ,measurement method ,skin and connective tissue diseases ,VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Kardiologi: 771 ,Public, Environmental & Occupational Health ,adult ,Population health ,public health ,blood pressure regulation ,Public Health, Global Health, Social Medicine and Epidemiology ,Non-communicable disease ,kansainvälinen vertailu ,health survey ,aged ,female ,priority journal ,Blood pressure ,mean arterial pressure ,GLOBAL TRENDS ,SODIUM-INTAKE ,Life Sciences & Biomedicine ,survey design ,hypertension ,prevalence ,Global health ,UNITED-STATES ,URBAN COMMUNITIES ,Article ,SECULAR TRENDS ,Middle East ,Central Asia ,male ,disease prevalence ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,kansanterveys ,blood ,SYSTEMATIC ANALYSIS ,human ,verenpainetauti ,non-communicable disease ,Science & Technology ,Pacific Ocean ,high income country ,diastolic blood pressure ,Pacific Rim ,Blood Pressure - Epidemiology - Population ,North Africa ,major clinical study ,HYPERTENSION PREVALENCE ,verenpaine ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,ARTERIAL-HYPERTENSION ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,POTASSIUM INTAKE ,sense organs ,trend analysis ,trend study ,population research ,population health ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,low income country - Abstract
Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group-and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups., This work was supported by the Wellcome Trust [101506/Z/13/Z].
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- 2018
7. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
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Winkler, Thomas W, Justice, Anne E, Graff, Mariaelisa, Barata, Llilda, Feitosa, Mary F, Chu, Su, Czajkowski, Jacek, Esko, Tõnu, Fall, Tove, Kilpeläinen, Tuomas O, Lu, Yingchang, Mägi, Reedik, Mihailov, Evelin, Pers, Tune H, Rüeger, Sina, Teumer, Alexander, Ehret, Georg B, Ferreira, Teresa, Heard-Costa, Nancy L, Karjalainen, Juha, Lagou, Vasiliki, Mahajan, Anubha, Neinast, Michael D, Prokopenko, Inga, Simino, Jeannette, Teslovich, Tanya M, Jansen, Rick, Westra, Harm-Jan, White, Charles C, Absher, Devin, Ahluwalia, Tarunveer S, Ahmad, Shafqat, Albrecht, Eva, Alves, Alexessander Couto, Bragg-Gresham, Jennifer L, de Craen, Anton JM, Bis, Joshua C, Bonnefond, Amélie, Boucher, Gabrielle, Cadby, Gemma, Cheng, Yu-Ching, Chiang, Charleston WK, Delgado, Graciela, Demirkan, Ayse, Dueker, Nicole, Eklund, Niina, Eiriksdottir, Gudny, Eriksson, Joel, Feenstra, Bjarke, Fischer, Krista, Frau, Francesca, Galesloot, Tessel E, Geller, Frank, Goel, Anuj, Gorski, Mathias, Grammer, Tanja B, Gustafsson, Stefan, Haitjema, Saskia, Hottenga, Jouke-Jan, Huffman, Jennifer E, Jackson, Anne U, Jacobs, Kevin B, Johansson, Åsa, Kaakinen, Marika, Kleber, Marcus E, Lahti, Jari, Mateo Leach, Irene, Lehne, Benjamin, Liu, Youfang, Lo, Ken Sin, Lorentzon, Mattias, Luan, Jian'an, Madden, Pamela AF, Mangino, Massimo, McKnight, Barbara, Medina-Gomez, Carolina, Monda, Keri L, Montasser, May E, Müller, Gabriele, Müller-Nurasyid, Martina, Nolte, Ilja M, Panoutsopoulou, Kalliope, Pascoe, Laura, Paternoster, Lavinia, Rayner, Nigel W, Renström, Frida, Rizzi, Federica, Rose, Lynda M, Ryan, Kathy A, Salo, Perttu, Sanna, Serena, Scharnagl, Hubert, Shi, Jianxin, Smith, Albert Vernon, Southam, Lorraine, Stančáková, Alena, Steinthorsdottir, Valgerdur, Strawbridge, Rona J, Sung, Yun Ju, Tachmazidou, Ioanna, Tanaka, Toshiko, Thorleifsson, Gudmar, Trompet, Stella, Pervjakova, Natalia, Tyrer, Jonathan P, Vandenput, Liesbeth, van der Laan, Sander W, van der Velde, Nathalie, van Setten, Jessica, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Vlachopoulou, Efthymia, Waite, Lindsay L, Wang, Sophie R, Wang, Zhaoming, Wild, Sarah H, Willenborg, Christina, Wilson, James F, Wong, Andrew, Yang, Jian, Yengo, Loïc, Yerges-Armstrong, Laura M, Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Andersson, Ehm A, Bakker, Stephan JL, Baldassarre, Damiano, Banasik, Karina, Barcella, Matteo, Barlassina, Cristina, Bellis, Claire, Benaglio, Paola, Blangero, John, Blüher, Matthias, Bonnet, Fabrice, Bonnycastle, Lori L, Boyd, Heather A, Bruinenberg, Marcel, Buchman, Aron S, Campbell, Harry, Chen, Yii-Der Ida, Chines, Peter S, Claudi-Boehm, Simone, Cole, John, Collins, Francis S, de Geus, Eco JC, de Groot, Lisette CPGM, Dimitriou, Maria, Duan, Jubao, Enroth, Stefan, Eury, Elodie, Farmaki, Aliki-Eleni, Forouhi, Nita G, Friedrich, Nele, Gejman, Pablo V, Gigante, Bruna, Glorioso, Nicola, Go, Alan S, Gottesman, Omri, Gräßler, Jürgen, Grallert, Harald, Grarup, Niels, Gu, Yu-Mei, Broer, Linda, Ham, Annelies C, Hansen, Torben, Harris, Tamara B, Hartman, Catharina A, Hassinen, Maija, Hastie, Nicholas, Hattersley, Andrew T, Heath, Andrew C, Henders, Anjali K, Hernandez, Dena, Hillege, Hans, Holmen, Oddgeir, Hovingh, Kees G, Hui, Jennie, Husemoen, Lise L, Hutri-Kähönen, Nina, Hysi, Pirro G, Illig, Thomas, De Jager, Philip L, Jalilzadeh, Shapour, Jørgensen, Torben, Jukema, J Wouter, Juonala, Markus, Kanoni, Stavroula, Karaleftheri, Maria, Khaw, Kay Tee, Kinnunen, Leena, Kittner, Steven J, Koenig, Wolfgang, Kolcic, Ivana, Kovacs, Peter, Krarup, Nikolaj T, Kratzer, Wolfgang, Krüger, Janine, Kuh, Diana, Kumari, Meena, Kyriakou, Theodosios, Langenberg, Claudia, Lannfelt, Lars, Lanzani, Chiara, Lotay, Vaneet, Launer, Lenore J, Leander, Karin, Lindström, Jaana, Linneberg, Allan, Liu, Yan-Ping, Lobbens, Stéphane, Luben, Robert, Lyssenko, Valeriya, Männistö, Satu, Magnusson, Patrik K, McArdle, Wendy L, Menni, Cristina, Merger, Sigrun, Milani, Lili, Montgomery, Grant W, Morris, Andrew P, Narisu, Narisu, Nelis, Mari, Ong, Ken K, Palotie, Aarno, Pérusse, Louis, Pichler, Irene, Pilia, Maria G, Pouta, Anneli, Rheinberger, Myriam, Ribel-Madsen, Rasmus, Richards, Marcus, Rice, Kenneth M, Rice, Treva K, Rivolta, Carlo, Salomaa, Veikko, Sanders, Alan R, Sarzynski, Mark A, Scholtens, Salome, Scott, Robert A, Scott, William R, Sebert, Sylvain, Sengupta, Sebanti, Sennblad, Bengt, Seufferlein, Thomas, Silveira, Angela, Slagboom, P Eline, Smit, Jan H, Sparsø, Thomas H, Stirrups, Kathleen, Stolk, Ronald P, Stringham, Heather M, Swertz, Morris A, Swift, Amy J, Syvänen, Ann-Christine, Tan, Sian-Tsung, Thorand, Barbara, Tönjes, Anke, Tremblay, Angelo, Tsafantakis, Emmanouil, van der Most, Peter J, Völker, Uwe, Vohl, Marie-Claude, Vonk, Judith M, Waldenberger, Melanie, Walker, Ryan W, Wennauer, Roman, Widén, Elisabeth, Willemsen, Gonneke, Wilsgaard, Tom, Wright, Alan F, Zillikens, M Carola, van Dijk, Suzanne C, van Schoor, Natasja M, Asselbergs, Folkert W, de Bakker, Paul IW, Beckmann, Jacques S, Beilby, John, Bennett, David A, Bergman, Richard N, Bergmann, Sven, Böger, Carsten A, Boehm, Bernhard O, Boerwinkle, Eric, Boomsma, Dorret I, Bornstein, Stefan R, Bottinger, Erwin P, Bouchard, Claude, Chambers, John C, Chanock, Stephen J, Chasman, Daniel I, Cucca, Francesco, Cusi, Daniele, Dedoussis, George, Erdmann, Jeanette, Eriksson, Johan G, Evans, Denis A, de Faire, Ulf, Farrall, Martin, Ferrucci, Luigi, Ford, Ian, Franke, Lude, Franks, Paul W, Froguel, Philippe, Gansevoort, Ron T, Gieger, Christian, Grönberg, Henrik, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Per, Hamsten, Anders, van der Harst, Pim, Hayward, Caroline, Heliövaara, Markku, Hengstenberg, Christian, Hicks, Andrew A, Hingorani, Aroon, Hofman, Albert, Hu, Frank, Huikuri, Heikki V, Hveem, Kristian, James, Alan L, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Kathiresan, Sekar, Kiemeney, Lambertus ALM, Kivimaki, Mika, Knekt, Paul B, Koistinen, Heikki A, Kooner, Jaspal S, Koskinen, Seppo, Kuusisto, Johanna, Maerz, Winfried, Martin, Nicholas G, Laakso, Markku, Lakka, Timo A, Lehtimäki, Terho, Lettre, Guillaume, Levinson, Douglas F, Lind, Lars, Lokki, Marja-Liisa, Mäntyselkä, Pekka, Melbye, Mads, Metspalu, Andres, Mitchell, Braxton D, Moll, Frans L, Murray, Jeffrey C, Musk, Arthur W, Nieminen, Markku S, Njølstad, Inger, Ohlsson, Claes, Oldehinkel, Albertine J, Oostra, Ben A, Palmer, Lyle J, Pankow, James S, Pasterkamp, Gerard, Pedersen, Nancy L, Pedersen, Oluf, Penninx, Brenda W, Perola, Markus, Peters, Annette, Polašek, Ozren, Pramstaller, Peter P, Psaty, Bruce M, Qi, Lu, Quertermous, Thomas, Raitakari, Olli T, Rankinen, Tuomo, Rauramaa, Rainer, Ridker, Paul M, Rioux, John D, Rivadeneira, Fernando, Rotter, Jerome I, Rudan, Igor, den Ruijter, Hester M, Saltevo, Juha, Sattar, Naveed, Schunkert, Heribert, Schwarz, Peter EH, Shuldiner, Alan R, Sinisalo, Juha, Snieder, Harold, Sørensen, Thorkild IA, Spector, Tim D, Staessen, Jan A, Stefania, Bandinelli, Thorsteinsdottir, Unnur, Stumvoll, Michael, Tardif, Jean-Claude, Tremoli, Elena, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, Verbeek, André LM, Vermeulen, Sita H, Viikari, Jorma S, Vitart, Veronique, Völzke, Henry, Vollenweider, Peter, Waeber, Gérard, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J, Watkins, Hugh, Zeggini, Eleftheria, arcOGEN Consortium, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Chakravarti, Aravinda, Clegg, Deborah J, Cupples, L Adrienne, Gordon-Larsen, Penny, Jaquish, Cashell E, Rao, DC, Abecasis, Goncalo R, Assimes, Themistocles L, Barroso, Inês, Berndt, Sonja I, Boehnke, Michael, Deloukas, Panos, Fox, Caroline S, Groop, Leif C, Hunter, David J, Ingelsson, Erik, Kaplan, Robert C, McCarthy, Mark I, Mohlke, Karen L, O'Connell, Jeffrey R, Schlessinger, David, Strachan, David P, Stefansson, Kari, van Duijn, Cornelia M, Hirschhorn, Joel N, Lindgren, Cecilia M, Heid, Iris M, North, Kari E, Borecki, Ingrid B, Kutalik, Zoltán, Loos, Ruth JF, Division of Statistical Genomics, Washington University School of Medicine, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Metabolic Science, MRC, Brown University, Center for Biological Sequence Analysis [Lyngby], Technical University of Denmark [Lyngby] (DTU), King‘s College London, Groningen Bioinformatics Centre, GBB, University of Groningen [Groningen], University of Queensland [Brisbane], National Institut of Food Science and Technology, University of Agriculture, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of neurology, Leiden University Medical Center (LUMC), University of Washington [Seattle], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Limnology, Ecology, Department of Ecology and Evolutionary Biology, University of California, Core Genotyping Facility, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Division of Cancer Epidemiology and Genetics, Institute of Health Sciences and Biocenter Oulu, University of Oulu, Department of Chemical Engineering Taiwan (DCET - NTHU), National Tsing Hua University [Hsinchu] (NTHU), University of Oxford [Oxford], Department of Epidemiology, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Departments of Epidemiology and Nutrition, Harvard School of Public Health, Department of Clinical Sciences, Lund University [Lund]-Lund University Diabetes Centre, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Department of Medical Sciences, Department of Educational Psychology and Counseling, National Taiwan Normal University (NTNU), Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE Genetics, deCODE genetics [Reykjavik], Interuniversity Cardiology Institute Netherlands, Molecular Genetics Section, University of Groningen [Groningen]-University Medical Centre Groningen, Kidney Center, University Medical Center Groningen [Groningen] (UMCG), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], Medical Department III, Universität Leipzig [Leipzig], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], GNS Science, Blackett Laboratory, Imperial College London, Medstar Research Institute, University of Rochester [USA], MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Dept Biochem & Mol Biol, Pennsylvania State University (Penn State), Penn State System-Penn State System, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Epidemiology, University Medical Centre Groningen, Unit for Molecular Epidemiology, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (KU), Faculty of Medicine, Institute of Public Health, Aalborg University [Denmark] (AAU), Department of Nutrition-Dietetics, Harokopio University of Athens, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, MRC National Survey of Health and Development, MRC Unit for Lifelong Health and Ageing, Department of Epidemiology and Public Health, University College of London [London] (UCL), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Research Center for Prevention and Health, Glostrup Hospital, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Cambridge Institute of Public Health, University of Cambridge [UK] (CAM), Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Queensland Institute of Medical Research, Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Head of Medical Sequencing, Department of Biostatistics, University of Washington, Department of Chronic Disease Prevention, Molecular Epidemiology, Department of Genetics, Université Laval [Québec] (ULaval), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Department of Internal Medicine, Université de Lausanne (UNIL), Carl Gustav Carus University Hospital, Loughborough University, Genomics and Bioinformatics Platform, Fondazione Filarete, Department of Medicine, Surgery, and Dentistry, University of Milano, Medizinische Klinik II, Universität zu Lübeck [Lübeck], Department of Genomic Medicine, University of Manchester [Manchester], The Wellcome Trust Centre for Human Genetics [Oxford], National Institutes of Health [Bethesda] (NIH), Department of Nephrology, University Medical Center, University of Groningen, Helmholtz-Zentrum München (HZM), Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Genetics and Pathology, Department of child and adolescent psychiatry, Universität Duisburg-Essen [Essen], Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, Germany, Universität Regensburg (UR), Franz-Volhard-Centrum für Klinische Forschung, ECRC, Department of Clinical Physiology, University of Tampere [Finland]-Tampere University Hospital, Finnish Institute of Occupational Health of Helsinki, Department of Clinical Chemistry, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Oncology, University of Tampere Medical School, University of Tampere, Department of Physiology, University of Eastern Finland-Institute of Biomedicine, Department of Medicine, Montreal, Developmental Brain and Behaviour Unit, University of Southampton, Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Centre for Bone and Arthritis Research, Institute of Medicine-University of Gothenburg (GU), Interdisciplinary Center for Psychiatric Epidemiology, Experimental Cardiology Laboratory, University Medical Center [Utrecht], Peter MacCallum Cancer Center, Faculty of Health Sciences, Aarhus University [Aarhus], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Department of Health Services, University of Washington, Group Health Research Institute, Group Health Cooperative, Department of Epidemiology, University of Washington, Department of Medicine, University of Washington, Cardiovascular Health Research Unit, University of Washington, The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku University Hospital (TYKS), Erasmus Medical Centre, Cedars-Sinai Medical Center, Department of Pathological Biochemistry, Royal Infirmary, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Institute of Preventive Medicine, Copenhagen University Hospital-Bispebjerg and Frederiksberg Hospitals, Maastricht University [Maastricht], Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Department of Epidemiology & Biostatistics, Radboud University Medical Center [Nijmegen], Institute for Community Medicine, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), MRC epidemiology Unit, Framingham Heart Study, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Metabolic Disease Group, University of Cambridge Metabolic Research Laboratories, Department of Genetics and Biotechnology, Wellcome Trust, Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Department of Epidemiology and Preventive Medicine, Regensburg University Medical Center, University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Department of Medical Genetics, Epidemiology Unit, Addenbrooke's Hospital-Medical Research Council (MRC), P30 AG010161/AG/NIA NIH HHS/United States, Psychiatry, Epidemiology and Data Science, NCA - Neurobiology of mental health, EMGO - Lifestyle, overweight and diabetes, APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Other departments, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, RS: CARIM - R3 - Vascular biology, MUMC+: DA BV AIOS Radiologie (9), Epidemiologie, Orthopedie, Institute for Molecular Medicine Finland, Helsinki Collegium for Advanced Studies, Behavioural Sciences, University of Helsinki, Transplantation Laboratory, Medicum, Research Programs Unit, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Marja-Liisa Lokki / Principal Investigator, Kardiologian yksikkö, Leif Groop Research Group, Quantitative Genetics, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Ehret, Georg Benedikt, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Universiteit Leiden-Universiteit Leiden, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of California (UC), University of Oxford, Lund University [Lund], Universität Leipzig, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Capital Region of Denmark, University of Copenhagen = Københavns Universitet (UCPH), Université de Lausanne = University of Lausanne (UNIL), Universität zu Lübeck = University of Lübeck [Lübeck], Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Gothenburg (GU)-Institute of Medicine, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Luan, Jian'an [0000-0003-3137-6337], Tyrer, Jonathan [0000-0003-3724-4757], Forouhi, Nita [0000-0002-5041-248X], Khaw, Kay-Tee [0000-0002-8802-2903], Langenberg, Claudia [0000-0002-5017-7344], Luben, Robert [0000-0002-5088-6343], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Apollo - University of Cambridge Repository, CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium, Biochemistry, Surgery, Internal Medicine, Public Health, Medical Oncology, Pathology, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, and Clinical Genetics
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0301 basic medicine ,Netherlands Twin Register (NTR) ,Male ,Cancer Research ,endocrine system diseases ,Biological pathways ,QH426-470 ,Genome ,Body Mass Index ,Body Size ,Genetics (clinical) ,ddc:616 ,Genetics & Heredity ,Sex Characteristics ,Loci ,MAGIC Consortium ,Mass index ,Age Factors ,Chromosome Mapping ,Middle Aged ,Genealogy ,Self-reported height ,Peripheral-blood ,Scale (social sciences) ,ICBP Consortium ,Female ,Life Sciences & Biomedicine ,Medical Genetics ,Research Article ,arcOGEN Consortium ,musculoskeletal diseases ,Adult ,European Continental Ancestry Group ,Natural menopause ,Aged ,Body Size/genetics ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Polymorphism, Single Nucleotide ,Waist-Hip Ratio ,Biology ,Body size ,DIAGRAM Consortium ,Age and sex ,White People ,Fat distribution ,GLGC Consortium ,03 medical and health sciences ,Life-course ,Genetics ,Weight-gain ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Medicinsk genetik ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,0604 Genetics ,Science & Technology ,nutritional and metabolic diseases ,Correction ,030104 developmental biology ,GWAS meta-analysis ,Global-BPGen Consortium ,Common SNPS ,CHARGE Consortium ,3111 Biomedicine ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR, Author Summary Adult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.
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8. Characteristics of medically attended influenza infection across age groups before the COVID-19 pandemic in Lebanon.
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Haddara A, Houry Z, Zahreddine N, Atallah M, Boutros CF, Tannous J, Sadaka C, Wehbe S, Kadi T, Ibrahim A, Ahmadieh R, Kardas T, Soudani N, Kalamouni HA, Zgheib Y, Yaman NE, Khafaja S, Lteif M, Shaker R, Casals AA, Youssef Y, Youssef N, Zein ZE, Chamseddine S, Chmaisse A, Haj M, Fayad D, Kiblawi S, Isaac I, Anan H, Radwan N, Wakim RH, Zaraket H, Kanj SS, and Dbaibo GS
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- Humans, Lebanon epidemiology, Male, Female, Retrospective Studies, Aged, Middle Aged, Adult, Risk Factors, Young Adult, Adolescent, Tertiary Care Centers statistics & numerical data, Child, Aged, 80 and over, Age Factors, Hospitalization statistics & numerical data, Child, Preschool, Coinfection epidemiology, Infant, Influenza B virus, SARS-CoV-2, Influenza A virus, Influenza, Human epidemiology, COVID-19 epidemiology
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Background: Influenza represents a significant global health burden for individuals and society. This study assessed the burden of medically attended influenza at a tertiary medical center in Lebanon to describe the demographics, risk factors, and outcomes prior to the COVID-19 pandemic., Methods: This was a retrospective review of patients who tested positive for the influenza virus during three seasons between July 1, 2016 to June 30, 2019, at the American University of Beirut Medical Center., Results: A total of 2049 patients who tested positive for influenza were analyzed. Influenza A accounted for 79.6 % of cases, and influenza B for 19.7 %, with influenza activity starting in October/November and peaking in December/January. Older age above 65 years (AOR=3.584), obesity (AOR=2.183), and chronic conditions such as chronic lung diseases (AOR=1.832), and bacterial co-infection (AOR= 2.834) were found to be independent risk factors for developing complications. Viral co-infection increased the likelihood of death tenfold. Vaccinated patients had a shorter mean hospital stay duration and a lower intensive care unit admission rate., Conclusion: The burden of medically attended influenza at our tertiary medical center in Lebanon prior to the COVID-19 pandemic was high. Vaccination decreased the likelihood of complications leading to intensive care unit admission in patients at risk., Competing Interests: Declaration of Competing Interest All the authors declare that they have no established conflicting financial interests or personal relationships that may have influenced the research presented in this paper., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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9. COVID-19 vaccine breakthrough infection among health care workers at MODHS hospitals in Saudi Arabia: A multicenter study.
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ELZahrany Y, Alamry A, AlGeer A, AlKhalifah H, AlGhamdi A, AlYateem I, Alateah S, Asghar N, and AlBarrak A
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- Humans, Female, Male, Saudi Arabia epidemiology, Retrospective Studies, Adult, Middle Aged, Vaccination statistics & numerical data, Hospitals statistics & numerical data, Breakthrough Infections, COVID-19 Vaccines administration & dosage, COVID-19 prevention & control, COVID-19 epidemiology, Health Personnel statistics & numerical data, SARS-CoV-2 immunology
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Background: We investigated the clinical manifestation and severity of COVID-19 infection represented as a composite outcome (hospital or ICU admission, or in-hospital death) among infected fully vaccinated HCWs, the RT-PCR test Ct value (Cycle Threshold) of positive fully vaccinated HCWs, and we measure the interval from the second vaccine to acquiring the infection., Methods: A multicenter retrospective cohort study was conducted in different regions at (16) Ministry of Defense Health Services (MODHS) hospitals. Data were restricted to fully vaccinated (minimum of 2 doses) HCWs who had a confirmed positive PCR test and employed in MODHS hospitals from August 2021 to March 2022., Results: A total of 45862 HCWs were vaccinated as of Aug 2021. Of these 1253 participants met the selection criteria and were included in the study. The average age of infected HCWs was 35.27 years (SD = ± 8.10) of which 57% were females. The HCWs were employed as doctors (24%), nurses (33%), and other (43%). The most administered vaccine type was mRNA (44%) followed by Adenovirus Viral Vector (39%) and mixed vaccine (17%). The incidence of COVID-19 vaccine breakthrough (BT) infection among HCWs was observed at 2.73% (m-RNA 3.19%, Viral Vector 2.83% and mixed 1.87%)., Conclusion: the overall COVID-19 (BT) infection incidence proportion was (2.73%), with the Mixed vaccine group showing the lowest (BT) incidence proportion (1.87%). The most commonly reported symptoms among (BT) infections were cough (51%), sore throat (51%), fever (47%), headache (31%), and runny nose (23%), with overall (6%) asymptomatic (BT) infections. We had (1%) hospital admissions, Zero ICU admission, and Zero deaths. our finding may indicate that infection affecting fully vaccinated patients were less severe and mostly affected the upper respiratory tract., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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10. Odoribacter splanchnicus bacteremia secondary to acute appendicitis: a case report with review of literature.
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Sasi S, Nair AP, Doiphode S, Gutti TS, Kolleri J, and Al-Maslamani M
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This report describes a rare instance of Odoribacter splanchnicus bacteremia secondary to acute appendicitis in a young man. Initially presenting with symptoms typical of appendicitis, he was diagnosed through clinical examination, laboratory tests, and computed tomography imaging, which confirmed an inflamed appendix with sealed perforation and abscess. O. splanchnicus , a Gram-negative anaerobe commonly found in the human gut, was identified as the causative agent through blood culture. The patient underwent successful laparoscopic appendectomy and was treated with intravenous amoxicillin-clavulanate, leading to a full recovery. This case highlights the potential of O. splanchnicus to act as an opportunistic pathogen in the context of intra-abdominal inflammation. It underscores the diagnostic challenges posed by O. splanchnicus , and the efficacy of advanced diagnostic tools like matrix-assisted laser desorption/ionization-time of flight mass spectrometry in identifying such rare infections., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)
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- 2024
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11. Unveiling rare and severe complications of respiratory viruses: A diverse case series of influenza A, influenza B, and Covid-19.
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Sasi S, Kolleri J, Ben Abid F, Thapur M, Nair AP, and Al-Maslamani M
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Competing Interests: The authors have no conflicts of interest to declare.
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- 2024
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12. Factors associated with immediate postoperative pulmonary complications after Appendectomies under general anesthesia: A retrospective analysis.
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Kumar N, Ayasa MA, Krishnadas CP, Chandra P, Al-Mustafa MM, Praveen S, Sinha T, and Sasi S
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Background: Postoperative pulmonary complications (PPC) include any complication that affects the respiratory system after anesthesia and surgery and are a significant cause of postoperative mortality and morbidity., Objectives: To describe the risk factors for immediate postoperative pulmonary complications after appendectomy under general anesthesia and to determine if rapid sequence induction decreases the risk., Design and Setting: A retrospective analysis of perioperative medical records of patients who underwent appendectomy under general anesthesia over a year, from January 1st, 2014, to December 31st, 2014, at Hamad General Hospital, Doha, Qatar, was done., Results: Of the 1005 patients who met the inclusion criteria, 27 (3.7%) had PPC. The incidence of PPC had a significant positive association with diabetes mellitus (DM), bronchial asthma (BA), number of intubation attempts, laparoscopic approach, and longer surgeries (>2 h). Hypertension, recent or ongoing upper respiratory tract infections, and smoking were not associated with an increased risk of PPC. Non-rapid sequence intubation (RSI) was not associated with an increased risk of PPC compared with RSI., Conclusions: The incidence of immediate PPC in ASA 1 and 2 appendectomy patients aged between 15 and 50 is significant. There is an increased risk among asthmatics, diabetics, and those with difficult airways. The RSI technique does not offer protection., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 Kumar, Ayasa, Krishnadas, Chandra, Al-Mustafa, Praveen, Sinha, Sasi, Licensee HBKU Press.)
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- 2023
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13. The role of IL-6, ferritin, and coagulopathy in Covid-19 clinical progression.
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Harahap AT, Irawan C, Susilo A, Harimurti K, Gathmyr D, Shatri H, Lubis AM, Nainggolan L, and Abdullah M
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- Humans, Disease Progression, Ferritins, Fibrinogen, Interleukin-6, Prospective Studies, SARS-CoV-2, Blood Coagulation Disorders etiology, COVID-19 complications
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Background In COVID-19, the release of pro-inflammatory mediators in the cytokine storm, primarily interleukin-6 (IL-6), has been hypothesized to induce pulmonary intravascular coagulation. However, the relationship between IL-6 and coagulopathy remains unclear in COVID-19 progression. We aimed to investigate the correlation of IL-6 with D-dimer, fibrinogen, prothrombin time (PT), and ferritin. Furthermore, we also analyzed the effect of those parameters on the worsening of COVID-19 patients. Methods A prospective cohort study was conducted in moderate and severe COVID-19 patients from June 2020 to January 2021. A serial evaluation of IL-6, D-dimer, fibrinogen, ferritin, and PT was performed and correlated with the patient's condition at admission and on the 14th day. The outcomes (improvement, worsening, or discharged patients) were recorded during the study. Results Of 374 patients, 73 study subjects (61 severe and 12 moderate COVID-19) were included in this study. A total of 35 out of 61 severe and one out of 12 moderate illness subjects had experienced worsening. Spearman-rank correlation of IL-6 with with ferritin, D-dimer, fibrinogen, and PT was 0.08 ( p =0.5), -0.13 ( p =0.27), 0.01 ( p =0.91), and 0.03 ( p =0.77), respectively. In ROC analysis, D-dimer (74,77%) and IL-6 (71,32%) were the highest among other variables (>60%). Conclusions In COVID-19 patients, there was a correlation between elevated IL-6 and D-dimer levels with disease deterioration. There was no correlation between elevated IL-6 levels with ferritin, D-dimer, fibrinogen, and PT levels. Therefore, changes in IL-6 and D-dimer can predict worsening in moderate and severe COVID-19 patients., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Harahap AT et al.)
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- 2023
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14. Antibodies against Histoplasma capsulatum and Aspergillus fumigatus among chronic TB patients in Indonesia: a cross-sectional study.
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Dewi IMW, Fauziah N, Ekawardhani S, Andriyoko B, Adawiyah R, Hartantri Y, Soeroto AY, Alisjahbana B, Denning DW, and Wahyuningsih R
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- Animals, Aspergillus fumigatus, Histoplasma, Cross-Sectional Studies, Indonesia, Sensitivity and Specificity, Antibodies, Sputum microbiology, Tuberculosis diagnosis, Tuberculosis veterinary, Mycobacterium tuberculosis
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Chronic pulmonary fungal infections may occur in patients with previous history of pulmonary tuberculosis (TB), and are often clinically misclassified as TB, especially when bacteriological confirmation for Mycobacterium tuberculosis is absent. In this study, we investigated the prevalence of antibody against Histoplasma capsulatum and Aspergillus fumigatus in patients with confirmed and clinically chronic TB. Antibodies against H. capsulatum and A. fumigatus were measured from serum samples using enzyme-linked immunosorbent assay (ELISA). The presence M. tuberculosis in sputum was confirmed using smear microscopy, GeneXpert MTB/RIF assay, or culture. Antibodies against H. capsulatum and A. fumigatus were elevated in 16.9% and 26.9% of bacteriologically confirmed chronic TB patients, and 12.1% and 18.2% in those without bacteriological confirmation, respectively. Approximately one-third of patients who had positive anti-Histoplasma antibody also had elevated levels of antibody against Aspergillus fumigatus (P < .001). Our study highlights the importance of chronic pulmonary fungal infection in post-TB patients with recurrent respiratory symptoms., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
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- 2023
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15. Endogenous endophthalmitis due to Serratia marcescens secondary to late-onset empyema Post-Cardiac surgery in an End-Stage renal disease patient on peritoneal dialysis.
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Sasi S, Faraj H, Barazi R, Kolleri J, Chitrambika P, Rahman Al Maslamani MA, and Ali M
- Abstract
Endogenous bacterial endophthalmitis results from bacterial seeding of the eye during bacteremia. A diagnosis of endogenous bacterial endophthalmitis requires clinical findings such as vitritis or hypopyon along with positive blood cultures. Serratia marcescens is the second most common pathogen causing hospital-acquired ocular infections. This report describes a case of endogenous bacterial endophthalmitis caused by S. marcescens in an older adult with end-stage renal disease (ESRD) on peritoneal dialysis, who had late-onset pleural empyema secondary to coronary artery bypass grafting (CABG). A 61-year-old gentleman presented with a two-day history of cloudy vision, black floaters, pain, swelling, and gradual vision loss in his right eye. There was no history of trauma, ocular surgeries, or previous similar episodes. He had myocardial infarction treated with CABG 3 months back. Examination showed a 3 mm hypopyon in the anterior chamber. He had classic signs of endophthalmitis with positive blood cultures for S. marcescens. He was treated with high-dose intravenous meropenem and intravitreal ceftazidime without vitrectomy. Endophthalmitis progressed to complete vision loss in his right eye, requiring evisceration. Endophthalmitis caused by S. marcescens is rare, but long-term outcomes can be severe, causing complete vision loss in about 60% of the patients. It is usually hospital-acquired, and the source can be late-onset empyema several months after cardiac surgery, in an immunocompromised patient. Systemic antibiotics should be supplemented with intravitreal agents with or without pars plana vitrectomy., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)
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- 2023
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16. Disseminated tuberculosis masquerading as Tolosa-Hunt syndrome in initial presentation: A case report with literature review.
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Sasi S, Nair AP, Kolleri J, Alzibdeh A, and Maslamani MSRA
- Abstract
Tolosa-Hunt syndrome (THS) is a painful ophthalmoplegia due to non-specific granulomatous inflammation in the cavernous sinus region. It is diagnosed by the International Classification of Headache Disorders (ICHD)-3 criteria. We report the case of a young lady who presented with a right-sided headache for 2 weeks, followed by right-sided diplopia for 4 days. Clinical examination revealed right trochlear nerve palsy. Magnetic resonance imaging (MRI) of her brain showed abnormal thickening and postcontrast enhancement of the right orbital apex and superior orbital fissure, suggesting THS. Examination of cerebrospinal fluid (CSF) ruled out intracranial infection. The initial presentation satisfied the ICHD-3 criteria. Further imaging revealed cervical, axillary, and intra-abdominal lymphadenopathy with granulomatous lesions in the spleen and right kidney. Ultrasound (US)-guided axillary lymph node biopsy was positive for Mycobacterium tuberculosis . QuantiFERON TB gold plus test from serum was positive. Based on radiological and histopathological findings, a diagnosis of disseminated tuberculosis involving lymph nodes, kidneys, spleen, and lungs was made. THS is a diagnosis of exclusion. This case signifies that patients diagnosed with THS based on ICHD-3 criteria should be extensively evaluated to rule out granulomatous infections such as tuberculosis. Typical THS symptoms with granulomatous inflammation can give false reassurance to clinicians and prevent investigation for more dangerous etiologies. As painful ophthalmoplegia can arise secondary to a myriad of pathologies, diagnostic workups for all possibilities should be exhausted before arriving at a diagnosis of THS. Regardless of MRI findings, workups for tuberculosis and fungal infections should be completed., (© 2023 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)
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- 2023
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17. Prolonged fever and exaggerated hypercoagulopathy in malaria vivax relapse and COVID-19 co-infection: a case report.
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Asmarawati TP, Martani OS, Bramantono B, and Arfijanto MV
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- Adult, Fever epidemiology, Humans, Male, Pandemics, Recurrence, Young Adult, COVID-19 diagnosis, Coinfection diagnosis, Coinfection epidemiology, Malaria complications, Malaria diagnosis, Malaria drug therapy, Malaria, Vivax epidemiology
- Abstract
Background: Coronavirus disease 2019 (COVID-19) often causes atypical clinical manifestations similar to other infectious diseases. In malaria-endemic areas, the pandemic situation will very likely result in co-infection of COVID-19 and malaria, although reports to date are still few. Meanwhile, this disease will be challenging to diagnose in areas with low malaria prevalence because the symptoms closely resemble COVID-19., Case Presentation: A 23-year-old male patient presented to the hospital with fever, anosmia, headache, and nausea 1 week before. He was diagnosed with COVID-19 and treated for approximately 10 days, then discharged to continue self-quarantine at home. 2 weeks later, he returned to the hospital with a fever raised intermittently every 2 days and marked by a chilling-fever-sweating cycle. A laboratory test for malaria and a nasopharyngeal swab for SARS CoV-2 PCR were conducted, confirming both diagnoses. The laboratory examination showed markedly elevated D-dimer. He was treated with dihydroartemisinin-piperaquine (DHP) 4 tablets per day for 3 days and primaquine 2 tablets per day for 14 days according to Indonesian National Anti-malarial Treatment Guidelines. After 6 days of treatment, the patient had no complaints, and the results of laboratory tests had improved. This report describes the key points in considering the differential diagnosis and prompt treatment of malaria infection during the pandemic of COVID-19 in an endemic country to prevent the worse clinical outcomes. COVID-19 and malaria may also cause a hypercoagulable state, so a co-infection of those diseases may impact the prognosis of the disease., Conclusion: This case report shows that considering the possibility of a co-infection in a COVID-19 patient who presents with fever can prevent delayed treatment that can worsen the disease outcome. Paying more attention to a history of travel to malaria-endemic areas, a history of previous malaria infection, and exploring anamnesis regarding the fever patterns in patients are important points in making a differential diagnosis of malaria infection during the COVID-19 pandemic., (© 2022. The Author(s).)
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- 2022
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18. Beware of the ambiguous enemy of multisystem inflammatory syndrome in adult (MIS-A) following Covid-19 infection or vaccination.
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Al Bishawi A, Ali M, Al-Zubaidi K, and Abdelhadi H
- Abstract
Multisystem Inflammatory Syndrome is a rare and novel clinical presentation described during the evolving COVID-19 pandemic. The condition is usually presenting as a sepsis-like syndrome leading to secondary multi-organ dysfunction post-COVID-19 infection. Although the syndrome has been mainly described in children, rare adults' form has been similarly described. We are describing a 37-year-old female patient presented with fever and neck pain after 1 month of a mild SARS-CoV-2 infection course and 10 days post her second COVID-19 vaccine. Examination demonstrated fever, hypotension, and hypoxemia, in addition to multiple tender cervical lymph nodes. Initial laboratory workup showed evidence of significant inflammation with raised markers, including C-reactive protein, ferritin, and interleukin-6. Extensive evaluation to rule out active infection was done, and all return negative, including repeat SARS-CoV-2 test. Furthermore, cardiac evaluation showed moderately reduced systolic ventricular function. Despite all negative test and supportive measures, the patient continued to deteriorate requiring critical care admission for ionotropic support, non-invasive ventilation in addition to presumptive broad-spectrum antimicrobial management. There was no significant improvement with supportive care until the presentation of multisystem involvement on in the context of a recent history of COVID 19 and negative infective screen was raised. The diagnosis of multisystem inflammatory syndrome-adult form (MIS-A) was embraced, and the patient was commenced on methylprednisolone leading to a dramatic resolution of symptoms both clinically and biochemically with stabilization of vital functions allowing for safe outcomes., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)
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- 2021
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19. Case Report: Fatal Viscerotropic Disease in a Young Woman Following Yellow Fever Vaccination.
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Brunaldi MO, Silva RJC, Fabro AT, de Almeida E Araujo DC, Basile-Filho A, Auxiliadora-Martins M, Menegueti MG, Beloddi MI, Alves Esposito DL, and Lopes da Fonseca BA
- Subjects
- Adult, Brain Edema pathology, Female, Hemorrhage pathology, Humans, Liver Failure, Acute pathology, Lung Diseases pathology, Brain Edema chemically induced, Hemorrhage chemically induced, Liver Failure, Acute chemically induced, Lung Diseases chemically induced, Yellow Fever prevention & control, Yellow Fever Vaccine adverse effects
- Abstract
Yellow fever is a viral hemorrhagic disease, and vaccination is the most effective way to minimize the impact of the disease. Serious adverse events after yellow fever vaccination are rare. We report the case of a young woman with an unusual presentation of yellow fever 17DD vaccine-associated acute viscerotropic disease, with severe hepatic impairment following a long incubation period. She died more than a month after yellow fever vaccination.
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- 2021
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20. Hematologic and coagulopathy parameter as a survival predictor among moderate to severe COVID-19 patients in non- ICU ward: a single-center study at the main referral hospital in Surabaya, East Java, Indonesia.
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Bintoro SUY, Dwijayanti NMI, Pramudya D, Amrita PN, Romadhon PZ, Asmarawati TP, Bachtiar A, and Hadi U
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- Adult, Aged, Hospitals, Humans, Indonesia, Intensive Care Units, Middle Aged, Referral and Consultation, Retrospective Studies, SARS-CoV-2, COVID-19
- Abstract
Background : This research aimed to examine and analyze risk factors for death, hematologic parameters and coagulation in COVID-19 patients at RSUD Dr. Soetomo Surabaya, one of the referral centers for probable COVID-19 patient cases in East Java. Method : This was a retrospective analytical study by taking secondary data on patients with probable COVID-19 cases who were treated in hospital isolation rooms from May to September, 2020. Result : Of 538 probable COVID-19 patients, 217 tested positive, with an average age of 52.11±13.12 years, and there were 38 death cases. Hematologic parameters, such as white blood cell, neutrophil and lymphocyte counts, were significantly different in the deceased group. On the other hand, coagulation parameters, consisting of D-dimer, CRP, PT, and aPTT showed significantly similar value in the deceased group. Univatiate analysis concluded that chronic kidney disease, diabetes mellitus, coronary heart disease, WBC, NLR, and PPT counts could predict the mortality, while multivariate analysis revealed that coronary heart disease was the only significant independent predictor of mortality. Conclusion : This research shows that hematologic and coagulation parameters were increased in the majority of COVID-19 patients and the deceased group. While the number of neutrophils and WBC increases, the number of lymphocytes decreases significantly with increasing disease severity. Coronary heart disease is an independent predictor of mortality., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Bintoro SUY et al.)
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- 2021
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21. Plasma cytokines during acute human fascioliasis.
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Aron-Said C, Montes M, White AC Jr, and Cabada MM
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- Animals, Child, Fasciola hepatica, Humans, Interleukin-5, Peru, Th17 Cells, Cytokines immunology, Fascioliasis immunology
- Abstract
Fascioliasis is a foodborne trematode endemic worldwide. Children under 15 years have the highest prevalence of infection. We hypothesized that acute fascioliasis would be associated with more pronounced cytokine changes than in chronic disease or no helminth infections. To test this hypothesis, 33 children who lived in the Peruvian highlands were classified into 3 groups: acute fascioliasis, chronic fascioliasis, and no helminth infection. Type Th1, Th2, and Th17 cytokines were measured in plasma by cytometric bead array. Children with acute infection had higher levels of IL-5 and IL-17 compared with controls (p < 0.001 and p < 0.007, respectively). The increased IL-5 plasma concentration in children with acute infection was associated with the eosinophilia found in that group., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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22. High rates of antimicrobial resistance among clinical isolates from microbiology laboratories in Syria.
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Karamya ZA, Youssef A, Adra A, Karah N, Kanj SS, Elamin W, Nahas RA, Shaddood A, Saleh A, Althiab E, and Abbara A
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacterial Proteins, Drug Resistance, Bacterial, Enterobacteriaceae drug effects, Hong Kong, Humans, Laboratories, Prevalence, Syria, beta-Lactamases, Methicillin-Resistant Staphylococcus aureus drug effects
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
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- 2021
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23. Co-cultivation of microbial sub-communities in microfluidic droplets facilitates high-resolution genomic dissection of microbial 'dark matter'.
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Tan JY, Wang S, Dick GJ, Young VB, Sherman DH, Burns MA, and Lin XN
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- Bioreactors, Coculture Techniques, Gastrointestinal Microbiome, Genomics, High-Throughput Nucleotide Sequencing, Humans, Microfluidics, Multigene Family, RNA, Ribosomal, 16S metabolism, Bacteria genetics, Metagenome, Metagenomics methods, Microbiological Techniques, Microbiota
- Abstract
While the 'unculturable' majority of the bacterial world is accessible with culture-independent tools, the inability to study these bacteria using culture-dependent approaches has severely limited our understanding of their ecological roles and interactions. To circumvent cultivation barriers, we utilize microfluidic droplets as localized, nanoliter-size bioreactors to co-cultivate subsets of microbial communities. This co-localization can support ecological interactions between a reduced number of encapsulated cells. We demonstrated the utility of this approach in the encapsulation and co-cultivation of droplet sub-communities from a fecal sample collected from a healthy human subject. With the whole genome amplification and metagenomic shotgun sequencing of co-cultivated sub-communities from 22 droplets, we observed that this approach provides accessibility to uncharacterized gut commensals for study. The recovery of metagenome-assembled genomes from one droplet sub-community demonstrated the capability to dissect the sub-communities with high-genomic resolution. In particular, genomic characterization of one novel member of the family Neisseriaceae revealed implications regarding its participation in fatty acid degradation and production of atherogenic intermediates in the human gut. The demonstrated genomic resolution and accessibility to the microbial 'dark matter' with this methodology can be applied to study the interactions of rare or previously uncultivated members of microbial communities., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2020
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24. Neutro"feels" lethal toxin.
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Mazgaeen L and Gurung P
- Subjects
- Antigens, Bacterial, Apoptosis Regulatory Proteins, Caspase 1, Macrophages, Bacterial Toxins
- Abstract
Discussion on lethal toxin-induced acute IL-1β production as dependent on NLRP1b and caspase-1, PAD4, cell-free DNA and neutrophils., (©2020 Society for Leukocyte Biology.)
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- 2020
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25. Aspergillus fumigatus -specific antibodies in patients with chronic tuberculosis.
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Dewi IMW, Soeroto AY, Putriyani G, Hanifah W, Permata A, Annisa J, Fithriyana I, Verweij PE, van Laarhoven A, de Veerdonk FLV, Alisjahbana B, and van Crevel R
- Subjects
- Antibodies, Fungal, Humans, Aspergillus fumigatus, Tuberculosis
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- 2020
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26. Viral Interference Between Dengue Virus and Hepatitis C Virus Infections.
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Liang PC, Chen KY, Huang CH, Chang K, Lu PL, Yeh ML, Huang CF, Huang CI, Hsieh MH, Dai CY, Lin ZY, Chen SC, Chuang WL, Chen YH, Huang JF, and Yu ML
- Abstract
Both dengue virus (DENV) and hepatitis C virus (HCV) belong to the Flaviviridae family and could induce hepatitis. We aimed to investigate the interference between them. In total, 515 patients confirmed with dengue fever (DF) were enrolled. Thirty-two patients (6.21%) were seropositive for anti-HCV; 12 of 32 anti-HCV-positive patients had detectable HCV-RNA at presentation of DF. The proportion of dengue hemorrhagic fever was comparable between patients with or without anti-HCV and between those with or without HCV-RNA. Eleven of 32 patients received HCV-RNA testing during a median interval of 23 months after DF, which revealed significantly increased HCV-RNA levels (5.43 ± 0.77 vs 3.09 ± 1.24 log IU/mL, follow-up vs acute-DF phase; P = .003). Four of 11 patients with baseline HCV-RNA values before DF demonstrated a nadir viremia during acute DF. We also included age-, sex-, and follow-up duration-matched HCV-monoinfected patients as controls; higher delta HCV-RNA changes were demonstrated in patients with DF than in controls during the follow-up period (2.34 ± 1.15 vs -0.27 ± 0.76 log IU/mL; P < .001). Further in vitro experiments showed that HCV nonstructural protein 5A was downregulated in Con1 HCV replicon cells infected by DENV1. These clinical and experimental findings suggested possible viral interference in DENV/HCV. However, HCV viremia did not affect the disease outcomes of DF., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2020
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27. Systemic Inflammatory Mediators Are Effective Biomarkers for Predicting Adverse Outcomes in Clostridioides difficile Infection.
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Dieterle MG, Putler R, Perry DA, Menon A, Abernathy-Close L, Perlman NS, Penkevich A, Standke A, Keidan M, Vendrov KC, Bergin IL, Young VB, and Rao K
- Subjects
- Adult, Aged, Animals, Biomarkers blood, Clostridioides difficile pathogenicity, Clostridium Infections blood, Disease Models, Animal, Female, Humans, Male, Mice, Middle Aged, Pilot Projects, Predictive Value of Tests, Prognosis, Prospective Studies, ROC Curve, Severity of Illness Index, Clostridium Infections diagnosis, Clostridium Infections mortality, Inflammation Mediators blood
- Abstract
Clostridioides difficile infection (CDI) can result in severe disease and death, with no accurate models that allow for early prediction of adverse outcomes. To address this need, we sought to develop serum-based biomarker models to predict CDI outcomes. We prospectively collected sera ≤48 h after diagnosis of CDI in two cohorts. Biomarkers were measured with a custom multiplex bead array assay. Patients were classified using IDSA severity criteria and the development of disease-related complications (DRCs), which were defined as ICU admission, colectomy, and/or death attributed to CDI. Unadjusted and adjusted models were built using logistic and elastic net modeling. The best model for severity included procalcitonin (PCT) and hepatocyte growth factor (HGF) with an area (AUC) under the receiver operating characteristic (ROC) curve of 0.74 (95% confidence interval, 0.67 to 0.81). The best model for 30-day mortality included interleukin-8 (IL-8), PCT, CXCL-5, IP-10, and IL-2Rα with an AUC of 0.89 (0.84 to 0.95). The best model for DRCs included IL-8, procalcitonin, HGF, and IL-2Rα with an AUC of 0.84 (0.73 to 0.94). To validate our models, we employed experimental infection of mice with C. difficile Antibiotic-treated mice were challenged with C. difficile and a similar panel of serum biomarkers was measured. Applying each model to the mouse cohort of severe and nonsevere CDI revealed AUCs of 0.59 (0.44 to 0.74), 0.96 (0.90 to 1.0), and 0.89 (0.81 to 0.97). In both human and murine CDI, models based on serum biomarkers predicted adverse CDI outcomes. Our results support the use of serum-based biomarker panels to inform Clostridioides difficile infection treatment. IMPORTANCE Each year in the United States, Clostridioides difficile causes nearly 500,000 gastrointestinal infections that range from mild diarrhea to severe colitis and death. The ability to identify patients at increased risk for severe disease or mortality at the time of diagnosis of C. difficile infection (CDI) would allow clinicians to effectively allocate disease modifying therapies. In this study, we developed models consisting of only a small number of serum biomarkers that are capable of predicting both 30-day all-cause mortality and adverse outcomes of patients at time of CDI diagnosis. We were able to validate these models through experimental mouse infection. This provides evidence that the biomarkers reflect the underlying pathophysiology and that our mouse model of CDI reflects the pathogenesis of human infection. Predictive models can not only assist clinicians in identifying patients at risk for severe CDI but also be utilized for targeted enrollment in clinical trials aimed at reduction of adverse outcomes from severe CDI., (Copyright © 2020 Dieterle et al.)
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- 2020
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28. Cryptosporidium parvum cyclic GMP-dependent protein kinase (PKG): An essential mediator of merozoite egress.
- Author
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Nava S, Sadiqova A, Castellanos-Gonzalez A, and White AC Jr
- Subjects
- Cell Line, Cryptosporidium parvum enzymology, Cryptosporidium parvum growth & development, Cyclic GMP-Dependent Protein Kinases antagonists & inhibitors, Cyclic GMP-Dependent Protein Kinases metabolism, Epithelial Cells parasitology, Gene Expression, Gene Silencing, Humans, Merozoites enzymology, Protozoan Proteins antagonists & inhibitors, Protozoan Proteins metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Cryptosporidium parvum genetics, Cyclic GMP-Dependent Protein Kinases genetics, Host-Parasite Interactions genetics, Merozoites genetics, Protozoan Proteins genetics
- Abstract
Cryptosporidiosis is an obligate intracellular pathogen causing diarrhea. Merozoite egress is essential for infection to spread between host cells. However, the mechanisms of egress have yet to be defined. We hypothesized that Cyclic GMP-Dependent Protein Kinase G (PKG) may be involved in Cryptosporidium egress. In this study, Cryptosporidium parvum PKG was silenced by using antisense RNA sequences. PKG-silencing significantly inhibited egress of merozoites from infected HCT-8 cells into the supernatant and led to retention of intracellular forms within the host cells. This data identifies PKG as a key mediator of merozoite egress, a key step in the parasite lifecycle., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2020
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29. Innate immune priming in the absence of TAK1 drives RIPK1 kinase activity-independent pyroptosis, apoptosis, necroptosis, and inflammatory disease.
- Author
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Malireddi RKS, Gurung P, Kesavardhana S, Samir P, Burton A, Mummareddy H, Vogel P, Pelletier S, Burgula S, and Kanneganti TD
- Subjects
- Animals, Caspase 8 immunology, Female, Inflammasomes immunology, Macrophages immunology, Mice, Mice, Knockout, Signal Transduction immunology, Apoptosis immunology, Immunity, Innate immunology, Inflammation immunology, MAP Kinase Kinase Kinases immunology, Necroptosis immunology, Pyroptosis immunology, Receptor-Interacting Protein Serine-Threonine Kinases immunology
- Abstract
RIPK1 kinase activity has been shown to be essential to driving pyroptosis, apoptosis, and necroptosis. However, here we show a kinase activity-independent role for RIPK1 in these processes using a model of TLR priming in a TAK1-deficient setting to mimic pathogen-induced priming and inhibition. TLR priming of TAK1-deficient macrophages triggered inflammasome activation, including the activation of caspase-8 and gasdermin D, and the recruitment of NLRP3 and ASC into a novel RIPK1 kinase activity-independent cell death complex to drive pyroptosis and apoptosis. Furthermore, we found fully functional RIPK1 kinase activity-independent necroptosis driven by the RIPK3-MLKL pathway in TAK1-deficient macrophages. In vivo, TAK1 inactivation resulted in RIPK3-caspase-8 signaling axis-driven myeloid proliferation and a severe sepsis-like syndrome. Overall, our study highlights a previously unknown mechanism for RIPK1 kinase activity-independent inflammasome activation and pyroptosis, apoptosis, and necroptosis (PANoptosis) that could be targeted for treatment of TAK1-associated myeloid proliferation and sepsis., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2019 Malireddi et al.)
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- 2020
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30. Stunting Is Preceded by Intestinal Mucosal Damage and Microbiome Changes and Is Associated with Systemic Inflammation in a Cohort of Peruvian Infants.
- Author
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Zambruni M, Ochoa TJ, Somasunderam A, Cabada MM, Morales ML, Mitreva M, Rosa BA, Acosta GJ, Vigo NI, Riveros M, Arango S, Durand D, Berends MN, Melby P, and Utay NS
- Subjects
- Child Development, Cohort Studies, Cytokines genetics, Cytokines metabolism, Feces microbiology, Female, Gene Expression Regulation, Growth Disorders epidemiology, Humans, Infant, Intestinal Diseases epidemiology, Male, Nutritional Status, Peru, Pilot Projects, Gastrointestinal Microbiome, Growth Disorders etiology, Intestinal Diseases pathology, Intestinal Mucosa pathology
- Abstract
Stunting, defined as height-for-age Z score equal to or lower than -2, is associated with increased childhood mortality, cognitive impairment, and chronic diseases. The aim of the study was to investigate the relationship between linear growth, intestinal damage, and systemic inflammation in infants at risk of stunting. We followed up 78 infants aged 5-12 months living in rural areas of Peru for 6 months. Blood samples for biomarkers of intestinal damage (intestinal fatty-acid-binding protein [I-FABP] and zonulin) and systemic inflammation (interleukin-1β, interleukin-6, tumor necrosis factor α [TNF-α], soluble CD14, and lipopolysaccharide-binding protein [LBP]) and fecal samples for microbiome analysis were collected at baseline and closure of the study. The children's growth and health status were monitored through biweekly home visits by trained staff. Twenty-one percent of the children became stunted: compared with non-stunted children, they had worse nutritional parameters and higher levels of serum I-FABP at baseline. The likelihood of becoming stunted was strongly associated with an increase in sCD14 over time; LBP and TNF-α showed a trend toward increase in stunted children but not in controls. The fecal microbiota composition of stunted children had an increased beta diversity compared with that of healthy controls throughout the study. The relative abundance of Ruminococcus 1 and 2 , Clostridium sensu stricto , and Collinsella increased in children becoming stunted but not in controls, whereas Providencia abundance decreased. In conclusion, stunting in our population was preceded by an increase in markers of enterocyte turnover and differences in the fecal microbiota and was associated with increasing levels of systemic inflammation markers.
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- 2019
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31. What Is Known About Candida auris.
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Bradley SF
- Published
- 2019
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32. Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis.
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Andersen BJ, Rosa BA, Kupritz J, Meite A, Serge T, Hertz MI, Curtis K, King CL, Mitreva M, Fischer PU, and Weil GJ
- Subjects
- Adolescent, Adult, Aged, Albendazole administration & dosage, Albendazole adverse effects, Antigens, Helminth blood, Cytokines blood, Cytokines immunology, Diethylcarbamazine adverse effects, Diethylcarbamazine therapeutic use, Elephantiasis, Filarial genetics, Elephantiasis, Filarial immunology, Female, Filaricides adverse effects, Humans, Ivermectin administration & dosage, Ivermectin adverse effects, Male, Middle Aged, Young Adult, Elephantiasis, Filarial drug therapy, Filaricides therapeutic use
- Abstract
Background: Lymphatic filariasis (LF) is a neglected tropical disease, and the Global Program to Eliminate LF delivers mass drug administration (MDA) to 500 million people every year. Adverse events (AEs) are common after LF treatment., Methodology/principal Findings: To better understand the pathogenesis of AEs, we studied LF-patients from a treatment trial. Plasma levels of many filarial antigens increased post-treatment in individuals with AEs, and this is consistent with parasite death. Circulating immune complexes were not elevated in these participants, and the classical complement cascade was not activated. Multiple cytokines increased after treatment in persons with AEs. A transcriptomic analysis was performed for nine individuals with moderate systemic AEs and nine matched controls. Differential gene expression analysis identified a significant transcriptional signature associated with post-treatment AEs; 744 genes were upregulated. The transcriptional signature was enriched for TLR and NF-κB signaling. Increased expression of seven out of the top eight genes upregulated in persons with AEs were validated by qRT-PCR, including TLR2., Conclusions/significance: This is the first global study of changes in gene expression associated with AEs after treatment of lymphatic filariasis. Changes in cytokines were consistent with prior studies and with the RNAseq data. These results suggest that Wolbachia lipoprotein is involved in AE development, because it activates TLR2-TLR6 and downstream NF-κB. Additionally, LPS Binding Protein (LBP, which shuttles lipoproteins to TLR2) increased post-treatment in individuals with AEs. Improved understanding of the pathogenesis of AEs may lead to improved management, increased MDA compliance, and accelerated LF elimination., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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33. Yellow Fever-induced Acute Lung Injury.
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Fabro AT, Engelman GG, Ferreira NN, Velloni JMF, Espósito DLA, da Fonseca BAL, and Brunaldi MO
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- Acute Lung Injury etiology, Adult, Autopsy, Fatal Outcome, Hemorrhage etiology, Humans, Lung Diseases etiology, Lung Diseases pathology, Male, Middle Aged, Time Factors, Yellow Fever complications, Acute Lung Injury pathology, Hemorrhage pathology, Yellow Fever pathology
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- 2019
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34. Visceral and Cutaneous Leishmaniases in a City in Syria and the Effects of the Syrian Conflict.
- Author
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Youssef A, Harfouch R, El Zein S, Alshehabi Z, Shaaban R, and Kanj SS
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cities, Databases, Factual, Female, Humans, Infant, Male, Middle Aged, Refugees, Syria epidemiology, Time Factors, Young Adult, Armed Conflicts, Leishmaniasis, Cutaneous epidemiology, Leishmaniasis, Visceral epidemiology
- Abstract
War provides ideal grounds for the outbreak of infectious diseases, and the Syrian war is not an exception to this rule. Following the civil crisis, Syria and refugee camps of neighboring countries witnessed an outbreak of leishmaniasis. We accessed the database of the central leishmaniasis registry in Latakia city and obtained the leishmaniasis data of the period 2008-2016. Our data showed that the years 2013 and 2014 recorded a surge in the number of both cutaneous leishmaniases (CL) and visceral leishmaniasis (VL) cases. This surge coincided with the massive internal displacement waves that struck Latakia governorate during that time. Subsequently, after 2015, the number of recorded CL and VL cases gradually decreased. This drop coincided with a reduced influx of internally displaced persons into Latakia governorate. Our report depicts the effects of the Syrian crisis on the epidemiology of leishmaniasis by outlining the experience of Latakia governorate. Similar results may have occurred in other refugee-hosting Syrian governorates.
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- 2019
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35. Distance learning in antimicrobial stewardship: innovation in medical education.
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Laks M, Guerra CM, Miraglia JL, and Medeiros EA
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- Anti-Bacterial Agents, Antimicrobial Stewardship organization & administration, Brazil, Drug Resistance, Microbial, Education, Distance organization & administration, Educational Measurement, Humans, Organizational Innovation, Students, Medical, Antimicrobial Stewardship methods, Education, Distance methods
- Abstract
Background: This study aimed to analyse the impact that web-based distance learning has on knowledge gain in medical students, as well as student perceptions of the methodology., Methods: This was an educational intervention study conducted at a tertiary teaching hospital in the city of São Paulo, Brazil. From 2008 to 2014, we offered a free web-based distance learning course, covering antimicrobial use and microbial resistance, to fifth-year medical students. The course encompassed 100 h of activities, with five theoretical modules, exercises and simulations, within a virtual learning environment. The students were tutored in their online activities, and some classes were conducted in real time for live discussions. In addition, students underwent face-to-face assessments of their knowledge of the topic before and after the course. Statistical analysis was performed and the means of the overall scores were obtained, as were the respective 95% confidence intervals (CIs). The means were compared by two-tailed paired t-tests and by the paired Wilcoxon test., Results: Of 814 eligible medical students, 606 (74.45%) completed the entire course during the study period. The mean score for knowledge of the topic was significantly higher on the final assessment than on the initial assessment (p < 0.001). We found that dedication (in hours) was directly proportional to the level of participation, as reflected in the mean final score (p = 0.009) and in the proportion of students who passed (p = 0.028). All of the participants considered their knowledge adequate or insufficient before the course, stating that it is quite important or important to address the topic during medical education. Although dedication levels were low, 70.5% stated that they had learned "quite a lot" or "more than expected" about the topic and would dedicate more time to it if they could., Conclusions: The use of a virtual learning environment can promote teaching and learning in the infectious diseases field, specifically for antimicrobial stewardship, increasing knowledge significantly, and should be considered for inclusion in the final stages of medical education.
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- 2019
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36. Cryptosporidium parvum Subtilisin-Like Serine Protease (SUB1) Is Crucial for Parasite Egress from Host Cells.
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Nava S, White AC Jr, and Castellanos-González A
- Subjects
- Humans, Cryptosporidiosis immunology, Cryptosporidium parvum growth & development, Cryptosporidium parvum immunology, Host-Parasite Interactions immunology, Oocytes growth & development, Oocytes immunology, Subtilisins immunology
- Abstract
Despite the severity and global burden of Cryptosporidium infection, treatments are less than optimal, and there is no effective vaccine. Egress from host cells is a key process for the completion of the life cycle of apicomplexan parasites. For Plasmodium species, subtilisin-like serine protease (SUB1) is a key mediator of egress. For Toxoplasma species, calcium-dependent protein kinases (CDPKs) are critical. In this study, we characterized Cryptosporidium SUB1 expression and evaluated its effect using an infection model. We found increased expression between 12 and 20 h after in vitro infection, prior to egress. We induced silencing of SUB1 (ΔSUB1) mRNA using SUB1 single-stranded antisense RNA coupled with human Argonaute 2. Silencing of SUB1 mRNA expression did not affect parasite viability, excystation, or invasion of target cells. However, knockdown led to a 95% decrease in the proportion of released merozoites in vitro ( P < 0.0001). In contrast, silencing of CDPK5 had no effect on egress. Overall, our results indicate that SUB1 is a key mediator of Cryptosporidium egress and suggest that interruption of the life cycle at this stage may effectively inhibit the propagation of infection., (Copyright © 2019 American Society for Microbiology.)
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- 2019
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37. Systematic sampling of adults as a sensitive means of detecting persistence of lymphatic filariasis following mass drug administration in Sri Lanka.
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Rao RU, Samarasekera SD, Nagodavithana KC, Punchihewa MW, Ranasinghe USB, and Weil GJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Animals, Female, Humans, Male, Mass Drug Administration, Middle Aged, Prevalence, Sri Lanka epidemiology, Surveys and Questionnaires, Young Adult, Albendazole administration & dosage, Diethylcarbamazine administration & dosage, Elephantiasis, Filarial drug therapy, Elephantiasis, Filarial epidemiology, Wuchereria bancrofti isolation & purification
- Abstract
Background: Sri Lanka's Anti-Filariasis Campaign conducted 5 annual rounds of mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole to eliminate lymphatic filariasis (LF) in all endemic districts between 2002 and 2006. Post-MDA surveillance has consistently documented Wuchereria bancrofti microfilaremia (Mf) rates below 1% in all sentinel and spot check sites since that time, and all implementation units easily satisfied WHO's target for school-based transmission assessment surveys (school-TAS) in 2013. However, more detailed studies have identified foci of persistent infection in the large coastal evaluation unit (EU) (population about 0.6 million) in Galle district. Therefore, the purpose of this study was to assess the sensitivity and feasibility of community-based TAS in adults (adult-TAS) and to compare results obtained by adult-TAS with prior school-TAS and molecular xenomonitoring (MX, molecular detection of filarial DNA in systematically sampled mosquitoes) results in this known problem area., Methodology and Principal Findings: Two cluster surveys were performed in independent samples of 30 evaluation areas (EAs) in the coastal Galle EU in 2015. Each survey tested approximately 1,800 adults for circulating filarial antigenemia (CFA) with the Alere Filariasis Test Strip. The CFA prevalence for all persons tested (N = 3,612) was 1.8% (CI 1.4-2.2), and this was significantly higher than the CFA rate of 0.4% obtained by school-TAS in 2013. CFA prevalences in the two samples were similar [1.5% (CI 1.0-2.2), and 2.0% (CI 1.4-2.7)]. Antigenemia prevalence in sampled EUs was highly variable (range 0-11%), and it exceeded 5% in 6 EAs. The 30 EAs sampled in one of our adult-TAS surveys had recently been assessed for persistent filariasis by molecular xenomonitoring (MX). CFA prevalence in adults and filarial DNA prevalence in mosquitoes in these EAs were significantly correlated (r = 0.43; P = 0.02)., Conclusions: Community based adult-TAS provided a reproducible measure of persistent W. bancrofti infection in a large evaluation unit in Sri Lanka that has low-level persistence of LF following multiple rounds of MDA. In addition, adult-TAS and MX results illustrate the focality of persistent LF in this setting. Adult-TAS may be more sensitive than school-TAS for this purpose. Adult-TAS and MX are potential options for post-MDA and post-validation surveillance programs to identify problem areas that require mop-up activities. Adult-TAS should also be useful for remapping areas with uncertain LF endemicity for possible inclusion in national LF elimination programs., Competing Interests: The authors have declared that no competing interests exist.
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- 2019
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38. Risk factors for lymphatic filariasis in two villages of the Democratic Republic of the Congo.
- Author
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Chesnais CB, Awaca-Uvon NP, Vlaminck J, Tambwe JP, Weil GJ, Pion SD, and Boussinesq M
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Democratic Republic of the Congo epidemiology, Elephantiasis, Filarial epidemiology, Female, Humans, Male, Middle Aged, Mosquito Nets, Occupational Exposure, Risk Factors, Sex Factors, Young Adult, Elephantiasis, Filarial etiology
- Abstract
Background: Little is known regarding risk factors for lymphatic filariasis (LF) in Central Africa. To expand on what is known, we studied the epidemiology of LF in two endemic villages in the Democratic Republic of the Congo., Methods: Dependent variables were Wuchereria bancrofti antigenaemia detected with filarial test strips (FTS) and microfilaraemia detected by night blood smears. The following factors were investigated: sex, age, the use of bednets, the use of latrines, hunting, fishing and agricultural activities, history of treatment with anthelmintic drugs, overnight stays in the bush, population density, the number of household members, and distance to rivers. Mixed multivariate logistic regression models were used., Results: Two hundred and fifty nine out of 820 (31.6%) of subjects aged ≥ 5 years had W. bancrofti antigenaemia and 11.8% (97/820) had microfilaraemia. Multivariable analysis of risk factors for antigenaemia demonstrated increased risk for males (aOR = 1.75, 95% CI: 1.20-2.53, P = 0.003), for older individuals (aOR = 9.12 in those aged > 35 years, 95% CI: 4.47-18.61, P < 0.001), for people not using bednets (aOR = 1.57, 95% CI: 1.06-2.33, P = 0.023), for farmers (aOR = 2.21, 95% CI: 1.25-3.90, P = 0.006), and for those who live close to a river (aOR = 2.78, 95% CI: 1.14-6.74, P = 0.024). Significant risk factors for microfilaraemia included age, male gender, overnight stay in the bush, and residence close to a river (aOR = 1.86, 2.01, 2.73; P = 0.011, 0.010, 0.041; for the three latter variables, respectively). People who reported having taken levamisole (n = 117) during the prior year had a significantly decreased risk of having filarial antigenaemia (aOR = 0.40, 95% CI: 0.21-0.76, P = 0.005)., Conclusions: Age, sex, not using bednets, and occupation-dependent exposure to mosquitoes were important risk factors for infection with W. bancrofti in this study. The association with levamisole use suggests that the drug may have prevented filarial infections. Other results suggest that transmission often occurs outside of the village. This study provides interesting clues regarding the epidemiology of LF in Central Africa.
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- 2019
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39. Mapping of lymphatic filariasis in loiasis areas: A new strategy shows no evidence for Wuchereria bancrofti endemicity in Cameroon.
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Wanji S, Esum ME, Njouendou AJ, Mbeng AA, Chounna Ndongmo PW, Abong RA, Fru J, Fombad FF, Nchanji GT, Ngongeh G, Ngandjui NV, Enyong PI, Storey H, Curtis KC, Fischer K, Fauver JR, Lew D, Goss CW, and Fischer PU
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Algorithms, Animals, Antibodies, Protozoan blood, Antigens, Protozoan analysis, Cameroon epidemiology, Child, Cross-Sectional Studies, Diagnostic Tests, Routine methods, Female, Humans, Immunoassay methods, Male, Middle Aged, Prevalence, Real-Time Polymerase Chain Reaction, Rural Population, Young Adult, Elephantiasis, Filarial epidemiology, Endemic Diseases, Loiasis epidemiology, Topography, Medical, Wuchereria bancrofti isolation & purification
- Abstract
Background: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate., Methodology/principal Findings: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses the same reagents as ICT) revealed an overall positivity rate of 1.1% and L. loa microfilaria (Mf) rates of up to 46%. Among the subjects with 0 to 8,000 Mf/ml in day blood, only 0.4% were FTS positive, while 22.2% of subjects with >8,000 Mf/ml were FTS positive. A Mf density of >8,200 Mf/ml was determined as the cut point at which positive FTS results should be excluded from the analysis. No FTS positive samples were also positive for W. bancrofti antibodies as measured by two different point of care tests that use the Wb123 antigen not found in L. loa. Night blood examination of the FTS positive subjects showed a high prevalence of L. loa Mf with densities up to 12,710 Mf/ml. No W. bancrofti Mf were identified, as confirmed by qPCR. Our results show that high loads of L. loa Mf in day blood are a reliable indicator of FTS positivity, and Wb123 rapid test proved to be relatively specific., Conclusions/significance: Our study provides a simple day blood-based algorithm for LF mapping in loiasis areas. The results indicate that many districts that were formerly classified as endemic for LF in Cameroon are non-endemic and do not require mass drug administration for elimination of LF., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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40. Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections.
- Author
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Dieterle MG, Rao K, and Young VB
- Subjects
- Drug Resistance, Bacterial drug effects, Drug Resistance, Bacterial genetics, Humans, Anti-Bacterial Agents therapeutic use, Clostridioides difficile genetics, Clostridioides difficile pathogenicity, Clostridium Infections drug therapy, Clostridium Infections genetics, Clostridium Infections pathology, Colitis drug therapy, Colitis genetics, Colitis microbiology, Diarrhea drug therapy, Diarrhea genetics, Diarrhea microbiology, Gastrointestinal Microbiome genetics, Microbiota genetics
- Abstract
Clostridium difficile is the leading infectious cause of antibiotic-associated diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the healthcare system, with nearly half a million infections yearly and an approximate 20% recurrence risk after successful initial therapy. The high incidence has driven new research on improved prevention such as the emerging use of probiotics, intestinal microbiome manipulation during antibiotic therapies, vaccinations, and newer antibiotics that reduce the disruption of the intestinal microbiome. While the treatment of acute C. difficile is effective in most patients, it can be further optimized by adjuvant therapies that improve the initial treatment success and decrease the risk of subsequent recurrence. Finally, the high risk of recurrence has led to multiple emerging therapies that target toxin activity, recovery of the intestinal microbial community, and elimination of latent C. difficile in the intestine. In summary, CDIs illustrate the complex interaction among host physiology, microbial community, and pathogen that requires specific therapies to address each of the factors leading to primary infection and recurrence., (© 2018 New York Academy of Sciences.)
- Published
- 2019
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41. Is it necessary to have a dentist within an intensive care unit team? Report of a randomised clinical trial.
- Author
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Bellissimo-Rodrigues WT, Menegueti MG, Gaspar GG, de Souza HCC, Auxiliadora-Martins M, Basile-Filho A, Martinez R, and Bellissimo-Rodrigues F
- Subjects
- Adult, Brazil, Female, Health Workforce, Hospitals, University, Humans, Male, Middle Aged, Nursing Staff, Hospital, Oral Hygiene, Respiratory Tract Infections prevention & control, Dental Care methods, Dental Staff, Hospital, Intensive Care Units, Oral Health, Patient Care Team
- Abstract
Objective: To evaluate the effectiveness of dental treatment in improving oral health in critical patients., Methods: This randomised clinical trial was conducted in a general intensive care unit (ICU) at a tertiary care public facility from 1 January 2011 to 8 August 2013. Data from 254 adult patients staying in the ICU for 48 hours or more were analysed. The experimental group (n = 127) had access to dental treatment provided by a dentist four to five times a week, in addition to routine oral hygiene, whereas the control group (n = 127) had access only to routine oral hygiene, including topical application of chlorhexidine, provided by the ICU nursing staff. The baseline oral health status of the enrolled patients was poor and included edentulism, caries, gingivitis, periodontitis and residual roots. Dental treatment consisted of toothbrushing, tongue scraping, removal of calculus, scaling and root planing, caries restoration and tooth extraction., Results: The Oral Hygiene Index Simplified (OHI-S) and Gingival Index (GI) scores decreased in the experimental group but did not change significantly in the control group during the ICU stay. Dental treatment prevented most of the episodes of respiratory tract infections, as previously reported. No severe adverse events from the dental treatment were observed., Conclusion: From an interprofessional perspective, our results support the idea of including dentists in the ICU team to improve oral health in critical patients and effectively prevent respiratory tract infections, in addition to the improvement achievable by applying chlorhexidine alone., (© 2018 FDI World Dental Federation.)
- Published
- 2018
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42. Socioeconomic Factors Associated with Fasciola hepatica Infection Among Children from 26 Communities of the Cusco Region of Peru.
- Author
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Cabada MM, Morales ML, Webb CM, Yang L, Bravenec CA, Lopez M, Bascope R, White AC, and Gotuzzo E
- Subjects
- Acute Disease epidemiology, Adolescent, Agriculture, Animals, Antibodies, Helminth blood, Child, Child, Preschool, Cross-Sectional Studies, Fasciola hepatica immunology, Fascioliasis immunology, Female, Humans, Logistic Models, Male, Peru epidemiology, Prevalence, Risk Factors, Rural Population statistics & numerical data, Fascioliasis epidemiology, Feces parasitology, Socioeconomic Factors
- Abstract
Fasciola hepatica is the most widely distributed trematode-affecting humans. The Andes Mountains are highly endemic for fascioliasis. We report results of a cross-sectional study evaluating the epidemiology of Fasciola among children in 26 agricultural communities in the Cusco region of Peru. Children 3 to 16 years old were enrolled in preschools and schools. Blood from participants was tested for complete blood counts, transaminases, and Fasciola antibodies. Stool samples were tested for Fasciola and other parasites. A total of 2,515 children were included in the analysis and the mean age was 9.6 years (±3.6). Ten percent (253) of the children had at least one positive test for Fasciola, 6% had chronic infection, and 0.4% acute infection. The rest of the subjects had only antibodies against Fasciola. The prevalence of infection varied from 0% to 20% between communities. Children with evidence of Fasciola exposure were older, lived at higher altitudes, and had a lower socioeconomic status than children without infection. The logistic regression analysis showed that children from Ancahuasi district, older children, and children with higher measures of poverty were more likely to have Fasciola exposure. Fascioliasis is common in the Cusco region and associated with poverty. However, the distribution varies markedly between communities.
- Published
- 2018
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43. Similar long-term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV-1-infected patients in a retrospective, real-life cohort of 14 years.
- Author
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Krznaric I, Bickel M, Carganico A, De Leuw P, Haberl A, Knecht G, Koegl C, Lauscher P, Schüttfort G, Stephan C, Wolf E, and Wolf T
- Subjects
- Adult, Aged, Aged, 80 and over, Female, HIV Infections virology, Humans, Male, Middle Aged, Prospective Studies, Protease Inhibitors pharmacology, Raltegravir Potassium pharmacology, Reverse Transcriptase Inhibitors pharmacology, Sustained Virologic Response, Treatment Outcome, Viral Load drug effects, Young Adult, HIV Infections drug therapy, HIV-1 drug effects, Protease Inhibitors administration & dosage, Raltegravir Potassium administration & dosage, Reverse Transcriptase Inhibitors administration & dosage
- Abstract
Objectives: Raltegravir is used in many antiretroviral combinations, but its use in treatment-experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative studies have shown a higher rate of virological failure. However, it has been used frequently for the management of treatment failure, as it was the first integrase inhibitor to become available, and thus offered new options for patients with multiple resistance. The strategic use of raltegravir in this setting is examined in this study., Methods: In order to examine the efficacy of raltegravir in second and later lines of antiretroviral combinations, data for 740 patients from three clinical cohorts were analysed with a focus on the combinations that were used. These were stratified into the combination of two nonnucleoside reverse transcriptase inhibitors and raltegravir (2NRTIs + RAL), the combination of a boosted protease inhibitor and raltegravir (bPI + RAL), and other raltegravir-containing combinations., Results: The overall rate of virological suppression to < 50 HIV-1 RNA copies/mL was 69.5%. Although the baseline rate of virological suppression was higher for 2NRTIs + RAL than for the other strata, the outcomes were similar for all three groups at weeks 24, 48, 72 and 96., Conclusions: These data indicate that, in a real-life setting, raltegravir can be used with a high virological success rate in treatment-experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression., (© 2018 British HIV Association.)
- Published
- 2018
- Full Text
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44. Allergic asthma: RIPK2 takes the lead.
- Author
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Poudel B and Gurung P
- Subjects
- Allergens, Animals, Inflammation, Asthma, Pyroglyphidae immunology
- Published
- 2018
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45. Novel treatment strategies and drugs in development for cryptosporidiosis.
- Author
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Chavez MA and White AC Jr
- Subjects
- Animals, Antiprotozoal Agents pharmacology, Clofazimine therapeutic use, Cryptosporidiosis epidemiology, Cryptosporidiosis parasitology, Diarrhea drug therapy, Diarrhea epidemiology, Diarrhea parasitology, Global Health, Humans, Immunocompromised Host, Mice, Nitro Compounds, Thiazoles therapeutic use, Antiprotozoal Agents administration & dosage, Cryptosporidiosis drug therapy, Drug Development
- Abstract
Introduction: Cryptosporidium is a protozoan pathogen that can cause diarrheal disease in healthy and immunosuppressed individuals, worldwide. Recent studies have highlighted the impact of cryptosporidiosis on children in resource-limited countries. Nitazoxanide is the only Food and Drug Administration approved treatment, but it is not consistently effective therapy for cryptosporidiosis in the most vulnerable populations. Areas covered: This review focused on recent published studies evaluating novel drugs and new compounds for the treatment of cryptosporidiosis. Expert commentary: Combinations of approved drugs have demonstrated some activity. Broad screens have demonstrated activity against Cryptosporidium for a number of available drugs, including statins and clofazimine, and the latter has advanced into clinical trials. Cryptosporidium calcium-dependent protein kinase 1 (CDPK1) has been identified as an attractive target for treatment, and bumped kinase inhibitors have been developed which inhibit CDPK1 and are active against Cryptosporidium growth both in vitro and in vivo. Inhibition of Plasmodium lipid kinase PI(4)K8 of Cryptosporidium by KDU731 greatly reduced oocyst shedding and improved diarrhea in calves with limited effects on the human PI(4)K. Another novel potent inhibitor MMV665917 was efficacious in mouse models with cidal activity against Cryptosporidium. Additional compounds have proved active in vitro. So far, only clofazimine has entered human trials.
- Published
- 2018
- Full Text
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46. Neglect of attention to reproductive health in women with HIV infection: contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study.
- Author
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Aebi-Popp K, Mercanti V, Voide C, Nemeth J, Cusini A, Jakopp B, Nicca D, Rasi M, Bruno A, Calmy A, and Martinez de Tejada B
- Subjects
- Adolescent, Adult, Cross-Sectional Studies, Family Planning Services methods, Family Planning Services organization & administration, Female, Humans, Middle Aged, Pregnancy, Surveys and Questionnaires, Switzerland, Young Adult, Contraceptive Agents therapeutic use, Drug Utilization statistics & numerical data, HIV Infections, Health Services Research, Pregnancy, Unplanned
- Abstract
Objectives: Women with HIV infection are mainly of reproductive age and need safe, effective and affordable contraception to avoid unintended pregnancies. The aim of this study was to evaluate contraceptive use and unintended pregnancies in this population in Switzerland., Methods: A self-report anonymous questionnaire on contraceptive methods, adherence to them, and unintended pregnancies was completed by women included in the Swiss HIV Cohort Study (SHCS) between November 2013 and June 2014. Sociodemographic characteristics and information related to combined antiretroviral therapy and HIV disease status were obtained from the SHCS database., Results: Of 462 women included, 164 (35.5%) reported not using any contraception. Among these, 65 (39.6%) reported being sexually active, although 29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the following methods were reported: condoms, 219 (73.5%); oral hormonal contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women on contraception, 32 (10.7%) reported using more than one contraceptive method and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16, oral contraception; four, other methods). Of these, 68.1% terminated the pregnancy and almost half (43.7%) continued using the same contraceptive method after the event., Conclusions: Family planning needs in HIV-positive women are not fully addressed because male condoms remained the predominant reported contraceptive method, with a high rate of unintended pregnancies. It is of utmost importance to provide effective contraception such as long-acting reversible contraceptives for women living with HIV., (© 2018 British HIV Association.)
- Published
- 2018
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47. Oncogenic Viruses in Skull Base Chordomas.
- Author
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Yakkioui Y, Speel EM, Van Overbeeke JJ, Boderie MJM, Pujari S, Hausen AZ, Wolffs PFG, and Temel Y
- Subjects
- Adult, Aged, DNA, Viral analysis, Female, Humans, Male, Middle Aged, Oncogenic Viruses, RNA, Viral analysis, Tumor Virus Infections virology, Chordoma virology, Skull Base Neoplasms virology, Tumor Virus Infections epidemiology
- Abstract
Background: Chordomas are rare tumors assumed to derive from notochordal remnants. We believe that a molecular switch is responsible for their malignant behavior. The involvement of oncogenic viruses has not been studied, however. Thus, in the present study, we investigated the presence of oncogenic viruses in chordomas., Methods: DNA and RNA from snap-frozen chordoma (n = 18) and chondrosarcoma (n = 15) specimens were isolated. Real-time PCR or RT-PCR was performed to assess the presence of multiple oncogenic viruses, including herpesviridea (herpes simplex virus [HSV]-1, HSV-2, Epstein-Barr virus [EBV], cytomegalovirus, human herpesvirus [HHV]- 6, HHV-7, and Kaposi's sarcoma-associated herpesvirus), polyomaviridea (parvovirus B19 [PVB19], BK virus, JC virus, Simian virus 40, Merkel cell polyomavirus, human polyomavirus [HPyV]-6, and HPyV-7), papillomaviridae, and respiratory viruses. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to validate the positive results., Results: PVB19 DNA was detected in 4 of 18 chordomas (22%) and in 1 of 15 chondrosarcomas (7%). IHC recognizing the VP2 capsid protein of PVB19 showed a positive cytoplasmic staining in 44% of the cases (14 of 32). HHV7 DNA was present in 6 of the 18 chordomas (33%). Genomic DNA of EBV was found in 22% of the samples; however, no positive results were found on ISH. None of the chordoma cases showed any presence of DNA from the remaining viruses., Conclusions: Viral involvement in the etiology of chordomas is likely, with PVB19 the most distinguishing., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
48. Impact of a multifaceted antimicrobial stewardship program: A front-line ownership driven quality improvement project in a large urban emergency department.
- Author
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Kaufman AJ, McCready J, and Powis J
- Subjects
- Humans, Ontario, Anti-Infective Agents therapeutic use, Antimicrobial Stewardship methods, Emergency Service, Hospital standards, Hospitals, Urban, Ownership, Quality Improvement
- Abstract
Background: Antibiotic overuse has promoted growing rates of antimicrobial resistance and secondary antibiotic-associated infections such as Clostridium difficile (C. difficile). Antimicrobial stewardship programs (ASPs) are effective in reducing antimicrobial use in the inpatient setting; however, the unique environment of the emergency department (ED) lends itself to challenges for successful implementation. Front-line ownership (FLO) methodology has been shown to be a potentially effective strategy for the implementation of inpatient ASPs through an iterative multi-pronged approach driven by front-line providers., Objective: To determine whether a FLO approach to antimicrobial stewardship in the ED can alter antimicrobial usage., Methods: Interventions were driven by ED physicians and facilitated by Infectious Diseases Division physicians from the hospital's ASP using FLO principles. Measured end points included antibiotic usage in the ED as measured by defined daily doses, and rates of urine culture sent from the ED., Results: There was a step-wise significant reduction in the use of azithromycin (p=0.006), ceftriaxone (p=0.045), ciprofloxacin (p=0.034), and moxifloxacin (p=0.008). There was also a significant reduction in rates of urine cultures (p<0.001) by 2.26 urine cultures per 100 ED patient visits., Conclusions: FLO offers a promising approach to successful implementation of an ASP in the ED. Future studies would be important to evaluate the generalizability of the FLO approach to ASP development in other EDs and to determine strategies to improve the sustainability of reductions in antimicrobial use.
- Published
- 2017
- Full Text
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49. Killing of Cryptosporidium sporozoites by Lactoferrin.
- Author
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Paredes JL, Sparks H, White AC Jr, Martinez-Traverso G, Ochoa T, and Castellanos-González A
- Subjects
- Humans, Lactoferrin chemistry, Milk, Human chemistry, Oocysts drug effects, Cryptosporidium drug effects, Lactoferrin pharmacology, Sporozoites drug effects
- Abstract
Intestinal infection caused by Cryptosporidium is a major contributor to diarrhea morbidity and mortality in young children around the world. Current treatments for children suffering from cryptosporidiosis are suboptimal. Lactoferrin is a glycoprotein found in breast milk. It has showed bacteriostatic and antimicrobial activity in the intestine. However, the effects of lactoferrin on the intestinal parasite Cryptosporidium have not been reported. In this study, we investigated the anticryptosporidial activity of human lactoferrin on different stages of Cryptosporidium . Physiologic concentrations of lactoferrin killed Cryptosporidium parvum sporozoites, but had no significant effect on oocysts viability or parasite intracellular development. Since sporozoites are essential for the infection process, our data reinforce the importance of breastfeeding and point to the potential of lactoferrin as a novel therapeutic agent for cryptosporidiosis.
- Published
- 2017
- Full Text
- View/download PDF
50. Recombinase Polymerase Amplification Compared to Real-Time Polymerase Chain Reaction Test for the Detection of Fasciola hepatica in Human Stool.
- Author
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Cabada MM, Malaga JL, Castellanos-Gonzalez A, Bagwell KA, Naeger PA, Rogers HK, Maharsi S, Mbaka M, and White AC Jr
- Subjects
- Animals, Fascioliasis parasitology, Humans, Microscopy, Sensitivity and Specificity, Fasciola hepatica genetics, Fascioliasis diagnosis, Feces parasitology, Nucleic Acid Amplification Techniques methods, Real-Time Polymerase Chain Reaction methods
- Abstract
Fasciola hepatica is the most widely distributed trematode infection in the world. Control efforts may be hindered by the lack of diagnostic capacity especially in remote endemic areas. Polymerase chain reaction (PCR)-based methods offer high sensitivity and specificity but require expensive technology. However, the recombinase polymerase amplification (RPA) is an efficient isothermal method that eliminates the need for a thermal cycler and has a high deployment potential to resource-limited settings. We report on the characterization of RPA and PCR tests to detect Fasciola infection in clinical stool samples with low egg burdens. The sensitivity of the RPA and PCR were 87% and 66%, respectively. Both tests were 100% specific showing no cross-reactivity with trematode, cestode, or nematode parasites. In addition, RPA and PCR were able to detect 47% and 26% of infections not detected by microscopy, respectively. The RPA adapted to a lateral flow platform was more sensitive than gel-based detection of the reaction products. In conclusion, the Fasciola RPA is a highly sensitive and specific test to diagnose chronic infection using stool samples. The Fasciola RPA lateral flow has the potential for deployment to endemic areas after further characterization., (© The American Society of Tropical Medicine and Hygiene.)
- Published
- 2017
- Full Text
- View/download PDF
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