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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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Author Correction: Identification of genetic effects underlying type 2 diabetes in South Asian and European populations

Communications biology

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Communications biology 2022年第1期5卷 441页

作者： Marie Loh Weihua Zhang Hong Kiat Ng Katharina Schmid Amel Lamri Lin Tong Meraj Ahmad Jung-Jin Lee Maggie C Y Ng Lauren E Petty Cassandra N Spracklen Fumihiko Takeuchi Md Tariqul Islam Farzana Jasmine Anuradhani Kasturiratne Muhammad Kibriya Karen L Mohlke Guillaume Paré Gauri Prasad Mohammad Shahriar Miao Ling Chee H Janaka de Silva James C Engert Hertzel C Gerstein K Radha Mani Charumathi Sabanayagam Marijana Vujkovic Ananda R Wickremasinghe Tien Yin Wong Chittaranjan S Yajnik Salim Yusuf Habibul Ahsan Dwaipayan Bharadwaj Sonia S Anand Jennifer E Below Michael Boehnke Donald W Bowden Giriraj R Chandak Ching-Yu Cheng Norihiro Kato Anubha Mahajan Xueling Sim Mark I McCarthy Andrew P Morris Jaspal S Kooner Danish Saleheen John C Chambers Lee Kong Chian School of Medicine Nanyang Technological University Singapore 308232 Singapore. Department of Epidemiology and Biostatistics Imperial College London London W2 1PG UK. Department of Cardiology Ealing Hospital London North West Healthcare NHS Trust Middlesex UB1 3HW UK. Institute of Computational Biology Deutsches Forschungszentrum für Gesundheit und Umwelt Helmholtz Zentrum München 85764 Neuherberg Germany. Department of Informatics Technical University of Munich 85748 Garching bei München Neuherberg Germany. Department of Medicine McMaster University Hamilton ON Canada. Population Health Research Institute Hamilton Health Sciences and McMaster University Hamilton ON Canada. The University of Chicago Biological Sciences Division Public Health Sciences 5841 South Maryland Avenue MC2000 Chicago IL 60637 USA. Genomic Research on Complex diseases CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB) Hyderabad India. Translational Medicine and Human Genetics Department of Medicine University of Pennsylvania Philadelphia Pennsylvania USA. Department of Medicine Mayo Hospital Lahore Pakistan. Center for Genomics and Personalized Medicine Research Center for Diabetes Research Wake Forest School of Medicine Winston-Salem NC 37215 USA. Vanderbilt Genetics Institute Division of Genetic Medicine Vanderbilt University Medical Center Nashville TN 37232 USA. Human Genetics Center School of Public Health The University of Texas Health Science Center at Houston Houston TX 77030 USA. Department of Genetics University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA. Department of Biostatistics and Epidemiology University of Massachusetts Amherst MA 01003 USA. Department of Gene Diagnostics and Therapeutics Research Institute National Center for Global Health and Medicine Tokyo Japan. U Chicago Research Bangladesh House#4 Road#2b Sector#4 Uttara Dhaka 1230 Bangladesh. Department of Public Health Faculty of Medicine

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ESICM LIVES 2016: part two

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Intensive Care Medicine Experimental 2016年第1期4卷 205-404页

作者： S. Sivakumar F. S. Taccone K. A. Desai C. Lazaridis M. Skarzynski M. Sekhon W. Henderson D. Griesdale L. Chapple A. Deane L. Williams R. Strickland K. Lange D. Heyland M. Chapman M. J. Rowland P. Garry J. Westbrook R. Corkill C. A. Antoniades K. T. Pattinson G. Fatania A. J. Strong R. B. Myers C. M. Jermaine C. S. Robertson C. G. Rusin J. Hofmeijer L. Sondag M. C. Tjepkema-Cloostermans A. Beishuizen F. H. Bosch M. J. A. M. van Putten L. Carteron C. Patet D. Solari M. Oddo M. A. Ali C. Dias R. Almeida A. Vaz-Ferreira J. Silva E. Monteiro A. Cerejo A. P. Rocha A. A. Elsayed A. M. Abougabal B. N. Beshey K. M. Alzahaby S. Pozzebon A. Blandino Ortiz S. Cristallini O. Lheureux A. Brasseur J. L. Vincent J. Creteur M. Hravnak K. Yousef Y. Chang E. Crago R. M. Friedlander S. A. Abdelmonem S. A. Tahon T. A. Helmy H. S. Meligy F. Puig I. Dunn-Siegrist J. Pugin S. Gupta D. Govil S. Srinivasan S. J. Patel J. K. N A. Gupta D. S. Tomar M. Shafi R. Harne D. P. Arora N. Talwar S. Mazumdar E. E. Papakrivou D. Makris E. Manoulakas B. Tsolaki B. Karadodas E. Zakynthinos I. Palacios Garcia A. Diaz Martin V. Sanchez Encinares M. Pachón Ibañez J. Garnacho Montero G. Labrador T. Cebrero Cangueiro V. Poulose J. Koh J. W. Kam H. Yeter A. Kara O. Aktepe A. Topeli I. Tsolakoglou G. Intas P. Stergiannis A. A. Kolaros E. Chalari E. Athanasiadou A. Martika G. Fildisis V. Faivre C. Mengelle B. Favier D. Payen A. Poppe M. S. Winkler E. Mudersbach J. Schreiber M. L. Wruck E. Schwedhelm S. Kluge C. Zöllner T. Tavladaki A. M. Spanaki H. Dimitriou E. Kondili C. Choulaki E. Meleti D. Kafetzopoulos D. Georgopoulos G. Briassoulis A. García-de la Torre M. V. de la Torre-Prados T. Tsvetanova-Spasova P. Nuevo-Ortega C. Rueda-Molina A. Fernández-Porcel E. Camara-Sola L. Salido-Díaz A. García-Alcántara D. E. Meleti B. Suberviola J. Riera L. Rellan M. Sanchez J. C. Robles E. Lopez R. Vicente E. Miñambres M. Santibañez M. Le Guen J. Moore N. Mason M. Windpassinger O. Plattner E. Mascha D. I. Sessler Outcomes Research U. Melia J. Fontanet J. P. van den Berg M. Baylor College of Medicine Neurology/Neurocritical Care Houston USA Erasmus Hospital Intensive Care Medicine Brussels Belgium Centre Hospitalier Régional Orléans Réaimation Médicale Orléans France University of British Columbia Vancouver Canada University of Adelaide Discipline of Acute Care Medicine Adelaide Australia Royal Adelaide Hospital Intensive Care Adelaide Australia Griffith University Menzies Health Institute of Queensland Gold Coast Australia University of Adelaide Discipline of Medicine Adelaide Australia Kingston General Hospital Clinical Evaluation Research Unit Kingston Canada University of Oxford Nuffield Department of Clinical Neurosciences Oxford UK Oxford University Hospitals NHS Foundation Trust Neurosciences Intensive Care Unit Oxford UK King’s College Hospital Department of Neurosurgery London UK King’ College London Institute of Psychiatry Psychology and Neuroscience Department of Clinical Neuroscience London UK Rice University Computer Science Houston USA Baylor College of Medicine Neurosurgery Houston USA Baylor College of Medicine Pediatric Cardiology Houston USA University of Twente Clinical Neurophysiology Enschede Netherlands Rijnstate Hospital Neurology Arnhem Netherlands Medical Spectrum Twente Clinical Neurophysiology Enschede Netherlands Medical Spectrum Twente Intensive Care Enschede Netherlands Rijnstate Hospital Intensive Care Arnhem Netherlands CHUV Department of Intensive Care Medicine Neuroscience Critical Care Research Group Lausanne Switzerland Aga Khan University Hospital Anaesthesiology Karachi Pakistan Centro Hospitalar São João Intensive Care Porto Portugal Faculty of Medicine University of Porto Medicine Porto Portugal Faculdade de Ciências Universidade do Porto Departamento de Matemática Porto Portugal Centro de Matemática Universidade do Porto Porto Portugal The Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine Zaragoza Spain Centro Hospitalar

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Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

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eClinicalMedicine 2023年 64卷 102193-102193页

作者： Wu, Dongze Jin, Yingzhao Xing, Yuhan Abate, Melsew Dagne Abbasian, Mohammadreza Abbasi-Kangevari, Mohsen Abbasi-Kangevari, Zeinab Abd-Allah, Foad Abdelmasseh, Michael Abdollahifar, Mohammad-Amin Abdulah, Deldar Morad Abedi, Aidin Abedi, Vida Abidi, Hassan Aboagye, Richard Gyan Abolhassani, Hassan Abuabara, Katrina Abyadeh, Morteza Addo, Isaac Yeboah Adeniji, Kayode Nelson Adepoju, Abiola Victor Adesina, Miracle Ayomikun Adnani, Qorinah Estiningtyas Sakilah Afarideh, Mohsen Aghamiri, Shahin Agodi, Antonella Agrawal, Anurag Arriagada, Constanza Elizabeth Aguilera Ahmad, Aqeel Ahmad, Danish Ahmad, Sohail Ahmadi, Ali Ahmed, Ayman Aithala, Janardhana P. Ajadi, Abdullateef Abiodun Ajami, Marjan Akbarzadeh-Khiavi, Mostafa Alahdab, Fares AlBataineh, Mohammad T. Alemi, Sharifullah Al-Gheethi, Adel Ali Saeed Ali, Liaqat Alif, Sheikh Mohammad Almazan, Joseph Uy Almustanyir, Sami Alqahtani, Jaber S. Alqasmi, Ibrahim Altaf, Ihsan Ullah Khan Alvis-Guzman, Nelson Alvis-Zakzuk, Nelson J. Al-Worafi, Yaser Mohammed Aly, Hany Amani, Reza Amu, Hubert Amusa, Ganiyu Adeniyi Andrei, Catalina Liliana Ansar, Adnan Ansariniya, Hossein Anyasodor, Anayochukwu Edward Arabloo, Jalal Arefnezhad, Reza Arulappan, Judie Asghari-Jafarabadi, Mohammad Ashraf, Tahira Atata, Jamila Abdulhamid Athari, Seyyed Shamsadin Atlaw, Daniel Atout, Maha Moh'd Wahbi Aujayeb, Avinash Awan, Asma Tahir Ayatollahi, Haleh Azadnajafabad, Sina Azzam, Ahmed Y. Badawi, Alaa Badiye, Ashish D. Bagherieh, Sara Baig, Atif Amin Bantie, Berihun Bantie Barchitta, Martina Bardhan, Mainak Barker-Collo, Suzanne Lyn Barone-Adesi, Francesco Batra, Kavita Bayileyegn, Nebiyou Simegnew Behnoush, Amir Hossein Belgaumi, Uzma Iqbal Bemanalizadeh, Maryam Bensenor, Isabela M. Beyene, Kebede A. Bhagavathula, Akshaya Srikanth Bhardwaj, Pankaj Bhaskar, Sonu Bhat, Ajay Nagesh Bitaraf, Saeid Bitra, Veera R. Boloor, Archith Bora, Kaustubh Botelho, João Silva Buchbinder, Rachelle Calina, Daniela Cámera, Luis Alberto Carvalho, Andre F. Chan, Jeffrey Shi Kai Chattu, Vijay Kumar Abebe, Endeshaw Chekol Department of Rheumatology and Immunology Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China China Department of Medicine & Therapeutics The Chinese University of Hong Kong Hong Kong Department of Paediatrics The Chinese University of Hong Kong Hong Kong School of Pharmacy The Chinese University of Hong Kong Hong Kong Jockey Club School of Public Health and Primary Care The Chinese University of Hong Kong Hong Kong Department of Nursing Woldia University Woldia Ethiopia Department of Orthopedic Surgery Harvard University Boston MA United States Postgraduate Medical Education Harvard University Boston MA United States Maternal Fetal Care Center Harvard University Boston MA United States Department of Health Policy and Oral Epidemiology Harvard University Boston MA United States Division of General Internal Medicine Harvard University Boston MA United States Department of Orthopaedic Surgery Shahid Beheshti University of Medical Sciences Tehran Iran Social Determinants of Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Department of Biotechnology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Epidemiology Shahid Beheshti University of Medical Sciences Tehran Iran National Nutrition and Food Technology Research Institute Shahid Beheshti University of Medical Sciences Tehran Iran Department of Immunology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Neurology Shahid Beheshti University of Medical Sciences Tehran Iran Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran Center for Comprehensive Genetic Services Shahid Beheshti University of Medical Sciences Tehran Iran Cancer Research Center Shahid Beheshti University of Medical Sciences Tehran Iran Department of Health Economics and Statistics Shahid Beheshti University of Medical Sciences Tehran Iran Functional Neuro

Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rh

关键词： Global burden of disease study Immune-mediated inflammatory disease Incidence Trend

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