Accès ouvert déclaré
2024
article
Genetic drivers of heterogeneity in type 2 diabetes pathophysiology
Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J. Taylor, Xianyong Yin, Kimberly Lorenz, Ravi Mandla, Alicia Huerta‐Chagoya, Giorgio E. M. Melloni, Stavroula Kanoni, Nigel William Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon Lee, Michael H Preuss, Lauren E. Petty, Philip H. Schroeder, Brett R. 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 Juan Parra, Jin Fang Chai, Lawrence F. Bielak, Yasuharu Tabara, Yang Hai, Guðmar Þorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo‐Heon Kwak, Jirong Long, Meng Sun, Tong Lin, Wei‐Min Chen, Suraj Singh Nongmaithem, Raymond Noordam, Victor 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 Kato 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 Alberto Aguilar-Salinas, Tarunveer S. Ahluwalia, Sonia S. Anand, Alain G. Bertoni, Jette Bork‐Jensen, Ivan Brandslund, Thomas A. Buchanan, Charles Burant, Adam S. Butterworth, Mickaël Canouil, Juliana C.N. Chan, Li-Ching Chang, Miao-Li Chee, Chen Ji, Shyh‐Huei Chen, Yuan‐Tsong Chen, Zhengming Chen, Lee‐Ming Chuang, Mary Cushman, John Danesh, Swapan K. Das, H. Janaka de Silva, George V. Dedoussis, Latchezar M. Dimitrov, Ayo Priscille 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 M. Genter, Hertzel C. Gerstein, Vilmantas Giedraitis, Clicerio González‐Villalpando, María Elena González-Villalpando, Penny Gordon‐Larsen, Myron D. Gross, Lindsay A. Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew Tym Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa A. Hsueh, Mengna Huang, Wei Huang, Yi‐Jen Hung, Mi Yeong Hwang, Chii‐Min Hwu, Sahoko Ichihara, M. Arfan Ikram, Martin Ingelsson, Md. Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost Bruno Jonas, Torben Jørgensen, Frederick Kamanu, FOUAD R. KANDEEL, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M. Keaton, Abel Kho, Chiea Chuen Khor, Muhammad Ghulam Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A. Lange, Kyung Min Lee, Myung‐Shik Lee, Nanette R. Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li‐Gao, Symen Ligthart, Cecilia M. Lindgren, Allan R Linneberg, Ching‐Ti Liu, Jianjun Liu, Adam E. Locke, Tin Louie, Jian’an Luan, Andrea O. Y. Luk, Xi Luo, Jun Lv, Julie Ann Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D. Morris, Filipe A. Moura, Jerry L. Nadler, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R. Patel, Snehal B. Patil, Pei Pei, Mark A. Pereira, Annette Peters, Fraser Pirie, Hannah G. Polikowsky, Bianca Porneala, Gauri Prasad, Laura J. Rasmussen‐Torvik, Alexander P. Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed A. Sattar, Sebastian G. Schönherr, Hasan Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A. Smith, Wing Yee So, Alena Stančáková, Valgerður Steinthórsdóttir, Adrienne M. Stilp, Konstantin Strauch, Kent D. Taylor, Barbara Thorand, Unnur Arna Thorsteinsdottir, Brian Tomlinson, Tam C. Tran, Fuu‐Jen Tsai, Jaakko Tuomilehto, Teresa Tusié‐Luna, Miriam S. Udler, Adán Valladares‐Salgado, Rob M. van Dam, Jan Bert van Klinken, Rohit Varma, Niels H. Wacher-Rodarte, Eleanor Wheeler, Ananda Rajitha Wickremasinghe, Ko Willems van Dijk, Daniel R. Witte, Chittaranjan Sakerlal Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian‐Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Stavroula Kanona, David A. van Heel, Leslie J. Raffel, Michiya Igase, Eli Ipp, Susan S Redline, Yoon Shin Cho, Lars Lind, Michael A. Province, Myriam Fornage, Craig L. Hanis, Erik Ingelsson, Alan B. Zonderman, Bruce M. Psaty, Ya Xing Wang, Charles N. Rotimi, Diane M. Becker, Fumihiko Matsuda, Mitsuhiro Yokota, Sharon L.R. Kardia, Patricia A. Peyser, James S. Pankow, James C. Engert, Amélie Bonnefond, Philippe Froguel, James Grant Wilson, Wayne Huey‐Herng Sheu, Jer‐Yuarn Wu, M. Geoffrey Hayes, C. W. Ronald, Tien Yin Wong, Dennis O. Mook‐Kanamori, Giriraj R. Chandak, Francis S. Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M. Sale, Habibul Ahsan, Ayesha Ahmed Motala, Xiao‐Ou Shu, Kyong Soo Park, J. Wouter Jukema, Miguel Cruz, Yii‐Der Ida Chen, Stephen S. Rich, Roberta McKean‐Cowdin, Harald Grallert, Ching‐Yu Cheng, Mohsen Ghanbari, E Shyong Tai, Josée Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon‐Puay Koh, Donald W. Bowden, Jaspal Singh Kooner, Charles Kooperberg, Simin Liu, Kari E. North, Danish Saleheen, Torben F. Hansen, Oluf Borbye Pedersen, Nicholas J. Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y. Millwood, Robin G. Walters, Kāri Stefánsson, Emma Ahlqvist, Mark O. Goodarzi, Karen L. Mohlke, Claudia Langenberg, Christopher A. Haiman, Ruth J. F. Loos, José C. Florez, Daniel J. Rader, Marylyn DeRiggi Ritchie, Sebastian K. Zöllner, Reedik Mägi, Nicholas Marston, Christian Thomas Ruff, Sarah Finer, Joshua C. Denny, Toshimasa Yamauchi, Takashi Kadowaki, John Campbell Chambers, Maggie Ng, Xueling Sim, Jennifer E. Below, Philip S. Tsao, Kyong‐Mi Chang, Mark I. McCarthy, James B. Meigs, Anubha Mahajan, Cassandra Nichole Spracklen, Josep Maria Mercader, Michael Boehnke, Jerome I. Rotter, Marijana Vujković, Benjamin Franklin Voight, Andrew Paul Morris, Eleftheria Zeggini
598Citations signalées, ce qui n’est pas une note de qualité
223Institutions déclarées
32Pays d’affiliation déclarés
Rattachement africain : gb, jp, de, us, cn, ee, kr, ca, sg, is, dk, nl, in, hk, tw, ir, se, mx, fr, lk, gr, fi, bd, ch, at, ph, no, Afrique du Sud, mo, sa, es, pk.
Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes 1,2 and molecular mechanisms that are often specific to cell type 3,4 . 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 −8 ) 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 5 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.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Genetic drivers of heterogeneity in type 2 diabetes pathophysiology
- Date Crossref
- 19/02/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Manchester
Division of Musculoskeletal and Dermatological Sciences
pays non établi dans la notice
Université ou école supérieure
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Arthritis UK
pays non établi dans la notice
Organisation à but non lucratif
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The University of Tokyo
pays non établi dans la notice
Université ou école supérieure
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The University of Osaka
pays non établi dans la notice
Université ou école supérieure
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Helmholtz Munich
pays non établi dans la notice
Structure de recherche
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National Institutes of Health
pays non établi dans la notice
Organisme public
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University of Cambridge
Department of Public Health and Primary Care
pays non établi dans la notice
Université ou école supérieure
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National Human Genome Research Institute
Center for Precision Health Research
pays non établi dans la notice
Structure de recherche
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University of Michigan
Department of Biostatistics and Center for Statistical Genetics
pays non établi dans la notice
Université ou école supérieure
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Statistical Research (United States)
pays non établi dans la notice
Entreprise
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Nanjing Medical University
pays non établi dans la notice
Université ou école supérieure
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Translational Therapeutics (United States)
pays non établi dans la notice
Entreprise
Division of Musculoskeletal and Dermatological Sciences — University of Manchester, Arthritis UK et The University of Tokyo, avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Les sujets associés
Genetic Associations and EpidemiologyEpigenetics and DNA MethylationCancer-related molecular mechanisms research