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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales

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Archives of virology 2021年第12期166卷 3567-3579页

作者： Jens H Kuhn Scott Adkins Bernard R Agwanda Rim Al Kubrusli Sergey V Alkhovsky Gaya K Amarasinghe Tatjana Avšič-Županc María A Ayllón Justin Bahl Anne Balkema-Buschmann Matthew J Ballinger Christopher F Basler Sina Bavari Martin Beer Nicolas Bejerman Andrew J Bennett Dennis A Bente Éric Bergeron Brian H Bird Carol D Blair Kim R Blasdell Dag-Ragnar Blystad Jamie Bojko Wayne B Borth Steven Bradfute Rachel Breyta Thomas Briese Paul A Brown Judith K Brown Ursula J Buchholz Michael J Buchmeier Alexander Bukreyev Felicity Burt Carmen Büttner Charles H Calisher Mengji Cao Inmaculada Casas Kartik Chandran Rémi N Charrel Qi Cheng Yuya Chiaki Marco Chiapello Il-Ryong Choi Marina Ciuffo J Christopher S Clegg Ian Crozier Elena Dal Bó Juan Carlos de la Torre Xavier de Lamballerie Rik L de Swart Humberto Debat Nolwenn M Dheilly Emiliano Di Cicco Nicholas Di Paola Francesco Di Serio Ralf G Dietzgen Michele Digiaro Olga Dolnik Michael A Drebot J Felix Drexler William G Dundon W Paul Duprex Ralf Dürrwald John M Dye Andrew J Easton Hideki Ebihara Toufic Elbeaino Koray Ergünay Hugh W Ferguson Anthony R Fooks Marco Forgia Pierre B H Formenty Jana Fránová Juliana Freitas-Astúa Jingjing Fu Stephanie Fürl Selma Gago-Zachert George Fú Gāo María Laura García Adolfo García-Sastre Aura R Garrison Thomas Gaskin Jean-Paul J Gonzalez Anthony Griffiths Tony L Goldberg Martin H Groschup Stephan Günther Roy A Hall John Hammond Tong Han Jussi Hepojoki Roger Hewson Jiang Hong Ni Hong Seiji Hongo Masayuki Horie John S Hu Tao Hu Holly R Hughes Florian Hüttner Timothy H Hyndman M Ilyas Risto Jalkanen Dàohóng Jiāng Gilda B Jonson Sandra Junglen Fujio Kadono Karia H Kaukinen Michael Kawate Boris Klempa Jonas Klingström Gary Kobinger Igor Koloniuk Hideki Kondō Eugene V Koonin Mart Krupovic Kenji Kubota Gael Kurath Lies Laenen Amy J Lambert Stanley L Langevin Benhur Lee Elliot J Lefkowitz Eric M Leroy Shaorong Li Longhui Li Jiànróng Lǐ Huazhen Liu Igor S Lukashevich Piet Maes William Marciel de Souza Marco Marklewitz Sergio H Marshall Shin-Yi L Marzano Se Integrated Research Facility at Fort Detrick National Institute of Allergy and Infectious Diseases National Institutes of Health Frederick MD USA. kuhnjens@mail.nih.gov. United States Department of Agriculture Agricultural Research Service US Horticultural Research Laboratory Fort Pierce FL USA. Zoology Department National Museums of Kenya Nairobi Kenya. Jomo Kenyatta University of Agriculture & Technology Nairobi Kenya. Division Phytomedicine Faculty of Life Sciences Humboldt-Universität zu Berlin Berlin Germany. D.I. Ivanovsky Institute of Virology of N.F. Gamaleya National Center on Epidemiology and Microbiology of Ministry of Health of Russian Federation Moscow Russia. Department of Pathology and Immunology Washington University School of Medicine St. Louis MO USA. Faculty of Medicine University of Ljubljana Ljubljana Slovenia. Centro de Biotecnología y Genómica de Plantas Universidad Politécnica de Madrid-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria Campus de Montegancedo Pozuelo de Alarcón Madrid Spain. Departamento de Biotecnología-Biología Vegetal Escuela Técnica Superior de Ingeniería Agronómica Alimentaria y de Biosistemas Universidad Politécnica de Madrid Madrid Spain. Center for Ecology of Infectious Diseases Department of Infectious Diseases Department of Epidemiology and Biostatistics Insitute of Bioinformatics University of Georgia Athens GA USA. Institute of Novel and Emerging Infectious Diseases Friedrich-Loeffler-Institut Federal Research Institute for Animal Health Greifswald-Insel Riems Germany. Department of Biological Sciences Mississippi State University Mississippi State MS USA. Center for Microbial Pathogenesis Institute for Biomedical Sciences Georgia State University Atlanta GA USA. Edge BioInnovation Consulting and Mgt Frederick MD USA. Institute of Diagnostic Virology Friedrich-Loeffler-Institut Greifswald-Insel Riems Germany. UFyMA INTA-CONICET Cordoba Argentina. Genomics and Bioinformatics D

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31st Annual Meeting and Associated programs of the Society for Immunotherapy of Cancer (SITC 2016): part one: National Harbor, MD, USA. 9-13 November 2016

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J Immunother Cancer 2016年第SUPPL 1期4卷 1-1页

作者： Andreas Lundqvist Vincent van Hoef Xiaonan Zhang Erik Wennerberg Julie Lorent Kristina Witt Laia Masvidal Sanz Shuo Liang Shannon Murray Ola Larsson Rolf Kiessling Yumeng Mao John-William Sidhom Catherine A. Bessell Jonathan Havel Jonathan Schneck Timothy A. Chan Eliot Sachsenmeier David Woods Anders Berglund Rupal Ramakrishnan Andressa Sodre Jeffrey Weber Roberta Zappasodi Yanyun Li Jingjing Qi Philip Wong Cynthia Sirard Michael Postow Walter Newman Henry Koon Vamsidhar Velcheti Margaret K. Callahan Jedd D. Wolchok Taha Merghoub Lawrence G. Lum Minsig Choi Archana Thakur Abhinav Deol Gregory Dyson Anthony Shields Cara Haymaker Marc Uemura Ravi Murthy Marihella James Daqing Wang Julie Brevard Catherine Monaghan Suzanne Swann James Geib Mark Cornfeld Srinivas Chunduru Sudhir Agrawal Cassian Yee Jennifer Wargo Sapna P. Patel Rodabe Amaria Hussein Tawbi Isabella Glitza Scott Woodman Wen-Jen Hwu Michael A. Davies Patrick Hwu Willem W. Overwijk Chantale Bernatchez Adi Diab Erminia Massarelli Neil H. Segal Vincent Ribrag Ignacio Melero Tara C. Gangadhar Walter Urba Dirk Schadendorf Robert L. Ferris Roch Houot Franck Morschhauser Theodore Logan Jason J. Luke William Sharfman Fabrice Barlesi Patrick A. Ott Laura Mansi Shivaani Kummar Gilles Salles Cecilia Carpio Roland Meier Suba Krishnan Dan McDonald Matthew Maurer Xuemin Gu Jaclyn Neely Satyendra Suryawanshi Ronald Levy Nikhil Khushalani Jennifer Wu Jinyu Zhang Fahmin Basher Mark Rubinstein Mark Bucsek Guanxi Qiao Cameron MacDonald Bonnie Hylander Elizabeth Repasky Shilpak Chatterjee Anusara Daenthanasanmak Paramita Chakraborty Kyle Toth Megan Meek Elizabeth Garrett-Mayer Michael Nishimura Chrystal Paulos Craig Beeson Xuezhong Yu Shikhar Mehrotra Fei Zhao Kathy Evans Christine Xiao Alisha Holtzhausen Brent A. Hanks Nicole Scharping Ashley V. Menk Rebecca Moreci Ryan Whetstone Rebekah Dadey Simon Watkins Robert Ferris Greg M. Delgoffe Jonathan Peled Sean Devlin Anna Staffas Melissa Lumish Kori Porosnicu Rodriguez Katya Ahr Miguel Perales Sergio Giralt Ying Taur Eric Pam Karolinska Institutet Stockholm Stockholms Lan Sweden Weill Cornell Medical College New York NY USA Nova Southeastern University Cell Therapy Institute Fort Lauderdale FL USA Johns Hopkins University School of Medicine Baltimore MD USA Immunology Program Johns Hopkins University School of Medicine Columbia MD USA Memorial Sloan Kettering Cancer Center New York NY USA Johns Hopkins Medical Institute Baltimore MD USA University of Rochester Monrovia MD USA NYU Langone Medical Center New York NY USA H. Lee Moffitt Cancer Center Tampa FL USA Ludwig Collaborative Laboratory Memorial Sloan Kettering Cancer Center New York NY USA Immune Monitoring Core Facility Memorial Sloan Kettering Cancer Center New York NY USA Leap Therapeutics Cambridge MA USA Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA Case Western Reserve University Cleveland OH USA Cleveland Clinic Main Campus Cleveland OH USA University of Virginia Cancer Center Charlottesville VA USA Stony Brook University Medical Center Stony Brook NY USA Karmanos Cancer Institute Detroit MI USA University of Texas MD Anderson Cancer Center Houston TX USA Idera Pharmaceuticals Inc. Cambridge MA USA Institut Gustave Roussy Villejuif Ile-de-France France Center for Applied Medical Research (CIMA) University of Navarra Pamplona Navarra Spain University of Pennsylvania Philadelphia PA USA Earle A. Chiles Research Institute Providence Cancer Center Portland OR USA Universitätsklinikum Essen Essen Nordrhein-Westfalen Germany University of Pittsburgh Pittsburgh PA USA CHU Rennes Service Hématologie Clinique and INSERM 0203 Unité d’Investigation Clinique Rennes Bretagne France Centre Hospitalier Régional Universitaire de Lille Lille Nord-Pas-de-Calais France Simon Cancer Center Indiana University Indianapolis IN USA University of Chicago School of Medicine Chicago IL USA Johns Hopkins University School of Medicine Lutherville MD USA Multidisciplinary Oncology and Therapeuti

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