2026-06-14T05:06:42Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/190672025-05-09T09:10:16Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19613

00925njm 22002777a 4500 dc Suzuki, Ken author Hatzikotoulas, Konstantinos author Southam, Lorraine author Taylor, Henry J author Yin, Xianyong author Lorenz, Kim M author Mandla, Ravi author Huerta-Chagoya, Alicia author Melloni, Giorgio E M author Kanoni, Stavroula author Rayner, Nigel W author Bocher, Ozvan author Arruda, Ana Luiza author Sonehara, Kyuto author Namba, Shinichi author Lee, Simon S K author Preuss, Michael H author Petty, Lauren E author Schroeder, Philip author Vanderwerff, Brett author Kals, Mart author Bragg, Fiona author Lin, Kuang author Guo, Xiuqing author Zhang, Weihua author Yao, Jie author Kim, Young Jin author Graff, Mariaelisa author Takeuchi, Fumihiko author Nano, Jana author Lamri, Amel author Nakatochi, Masahiro author Moon, Sanghoon author Scott, Robert A author Cook, James P author Lee, Jung-Jin author Pan, Ian author Taliun, Daniel author Parra, Esteban J author Chai, Jin-Fang author Bielak, Lawrence F author Tabara, Yasuharu author Hai, Yang author Thorleifsson, Gudmar author Grarup, Niels author Sofer, Tamar author Wuttke, Matthias author Sarnowski, Chloé author Gieger, Christian author Nousome, Darryl author Trompet, Stella author Kwak, Soo-Heon author Long, Jirong author Sun, Meng author Tong, Lin author Chen, Wei-Min author Nongmaithem, Suraj S author Noordam, Raymond author Lim, Victor J Y author Tam, Claudia H T author Joo, Yoonjung Yoonie author Chen, Chien-Hsiun author Raffield, Laura M author Prins, Bram Peter author Nicolas, Aude author Yanek, Lisa R author Chen, Guanjie author Brody, Jennifer A author Kabagambe, Edmond author An, Ping author Xiang, Anny H author Choi, Hyeok Sun author Cade, Brian E author Tan, Jingyi author Broadaway, K Alaine author Williamson, Alice author Kamali, Zoha author Cui, Jinrui author Thangam, Manonanthini author Adair, Linda S author Adeyemo, Adebowale author Aguilar-Salinas, Carlos A author Ahluwalia, Tarunveer S author Anand, Sonia S author Bertoni, Alain author Bork-Jensen, Jette author Brandslund, Ivan author Buchanan, Thomas A author Burant, Charles F author Butterworth, Adam S author Canouil, Mickaël author Chan, Juliana C N author Chang, Li-Ching author Chee, Miao-Li author Chen, Ji author Chen, Shyh-Huei author Chen, Yuan-Tsong author Chen, Zhengming author Chuang, Lee-Ming author Cushman, Mary author Danesh, John author Das, Swapan K author de Silva, H Janaka author Dedoussis, George author Dimitrov, Latchezar author Doumatey, Ayo P author Du, Shufa author Duan, Qing author Eckardt, Kai-Uwe author Emery, Leslie S author Evans, Daniel S author Evans, Michele K author Fischer, Krista author Floyd, James S author Ford, Ian author Franco, Oscar H author Frayling, Timothy M author Freedman, Barry I author Genter, Pauline author Gerstein, Hertzel C author Giedraitis, Vilmantas author González-Villalpando, Clicerio author González-Villalpando, Maria Elena author Gordon-Larsen, Penny author Gross, Myron author Guare, Lindsay A author Hackinger, Sophie author Hakaste, Liisa author Han, Sohee author Hattersley, Andrew T author Herder, Christian author Horikoshi, Momoko author Howard, Annie-Green author Hsueh, Willa author Huang, Mengna author Huang, Wei author Hung, Yi-Jen author Hwang, Mi Yeong author Hwu, Chii-Min author Ichihara, Sahoko author Ikram, Mohammad Arfan author Ingelsson, Martin author Islam, Md Tariqul author Isono, Masato author Jang, Hye-Mi author Jasmine, Farzana author Jiang, Guozhi author Jonas, Jost B author Jørgensen, Torben author Kamanu, Frederick K author Kandeel, Fouad R author Kasturiratne, Anuradhani author Katsuya, Tomohiro author Kaur, Varinderpal author Kawaguchi, Takahisa author Keaton, Jacob M author Kho, Abel N author Khor, Chiea-Chuen author Kibriya, Muhammad G author Kim, Duk-Hwan author Kronenberg, Florian author Kuusisto, Johanna author Läll, Kristi author Lange, Leslie A author Lee, Kyung Min author Lee, Myung-Shik author Lee, Nanette R author Leong, Aaron author Li, Liming author Li, Yun author Li-Gao, Ruifang author Ligthart, Symen author Lindgren, Cecilia M author Linneberg, Allan author Liu, Ching-Ti author Liu, Jianjun author Locke, Adam E author Louie, Tin author Luan, Jian'an author Luk, Andrea O author Luo, Xi author Lv, Jun author Lynch, Julie A author Lyssenko, Valeriya author Maeda, Shiro author Mamakou, Vasiliki author Mansuri, Sohail Rafik author Matsuda, Koichi author Meitinger, Thomas author Melander, Olle author Metspalu, Andres author Mo, Huan author Morris, Andrew D author Moura, Filipe A author Nadler, Jerry L author Nalls, Michael A author Nayak, Uma author Ntalla, Ioanna author Okada, Yukinori author Orozco, Lorena author Patel, Sanjay R author Patil, Snehal author Pei, Pei author Pereira, Mark A author Peters, Annette author Pirie, Fraser J author Polikowsky, Hannah G author Porneala, Bianca author Prasad, Gauri author Rasmussen-Torvik, Laura J author Reiner, Alexander P author Roden, Michael author Rohde, Rebecca author Roll, Katheryn author Sabanayagam, Charumathi author Sandow, Kevin author Sankareswaran, Alagu author Sattar, Naveed author Schönherr, Sebastian author Shahriar, Mohammad author Shen, Botong author Shi, Jinxiu author Shin, Dong Mun author Shojima, Nobuhiro author Smith, Jennifer A author So, Wing Yee author Stančáková, Alena author Steinthorsdottir, Valgerdur author Stilp, Adrienne M author Strauch, Konstantin author Taylor, Kent D author Thorand, Barbara author Thorsteinsdottir, Unnur author Tomlinson, Brian author Tran, Tam C author Tsai, Fuu-Jen author Tuomilehto, Jaakko author Tusié-Luna, Teresa author Udler, Miriam S author Valladares-Salgado, Adan author van Dam, Rob M author van Klinken, Jan B author Varma, Rohit author Wacher-Rodarte, Niels author Wheeler, Eleanor author Wickremasinghe, Ananda R author van Dijk, Ko Willems author Witte, Daniel R author Yajnik, Chittaranjan S author Yamamoto, Ken author Yamamoto, Kenichi author Yoon, Kyungheon author Yu, Canqing author Yuan, Jian-Min author Yusuf, Salim author Zawistowski, Matthew author Zhang, Liang author Zheng, Wei author Raffel, Leslie J author Igase, Michiya author Ipp, Eli author Redline, Susan author Cho, Yoon Shin author Lind, Lars author Province, Michael A author Fornage, Myriam author Hanis, Craig L author Ingelsson, Erik author Zonderman, Alan B author Psaty, Bruce M author Wang, Ya-Xing author Rotimi, Charles N author Becker, Diane M author Matsuda, Fumihiko author Liu, Yongmei author Yokota, Mitsuhiro author Kardia, Sharon L R author Peyser, Patricia A author Pankow, James S author Engert, James C author Bonnefond, Amélie author Froguel, Philippe author Wilson, James G author Sheu, Wayne H H author Wu, Jer-Yuarn author Hayes, M Geoffrey author Ma, Ronald C W author Wong, Tien-Yin author Mook-Kanamori, Dennis O author Tuomi, Tiinamaija author Chandak, Giriraj R author Collins, Francis S author Bharadwaj, Dwaipayan author Paré, Guillaume author Sale, Michèle M author Ahsan, Habibul author Motala, Ayesha A author Shu, Xiao-Ou author Park, Kyong-Soo author Jukema, J Wouter author Cruz, Miguel author Chen, Yii-Der Ida author Rich, Stephen S author McKean-Cowdin, Roberta author Grallert, Harald author Cheng, Ching-Yu author Ghanbari, Mohsen author Tai, E-Shyong author Dupuis, Josée author Kato, Norihiro author Laakso, Markku author Köttgen, Anna author Koh, Woon-Puay author Bowden, Donald W author Palmer, Colin N A author Kooner, Jaspal S author Kooperberg, Charles author Liu, Simin author North, Kari E author Saleheen, Danish author Hansen, Torben author Pedersen, Oluf author Wareham, Nicholas J author Lee, Juyoung author Kim, Bong-Jo author Millwood, Iona Y author Walters, Robin G author Stefansson, Kari author Ahlqvist, Emma author Goodarzi, Mark O author Mohlke, Karen L author Langenberg, Claudia author Haiman, Christopher A author Loos, Ruth J F author Florez, Jose C author Rader, Daniel J author Ritchie, Marylyn D author Zöllner, Sebastian author Mägi, Reedik author Marston, Nicholas A author Ruff, Christian T author van Heel, David A author Finer, Sarah author Denny, Joshua C author Yamauchi, Toshimasa author Kadowaki, Takashi author Chambers, John C author Ng, Maggie C Y author Sim, Xueling author Below, Jennifer E author Tsao, Philip S author Chang, Kyong-Mi author McCarthy, Mark I author Meigs, James B author Mahajan, Anubha author Spracklen, Cassandra N author Mercader, Josep M author Boehnke, Michael author Rotter, Jerome I author Vujkovic, Marijana author Voight, Benjamin F author Morris, Andrew P author Zeggini, Eleftheria author 2024-03 Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. 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 scores5 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. Nature. 2024 Mar;627(8003):347-357. 10.1038/s41586-024-07019-6 1476-4687 Nature 38374256 http://hdl.handle.net/20.500.12105/19067 Genetic drivers of heterogeneity in type 2 diabetes pathophysiology