Pulse Brain · Growing Health Evidence Index
Peer-reviewed

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 Melloni, Stavroula Kanoni, Nigel W. Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon Lee, Michael 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, 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 S. Nongmaithem, Raymond Noordam, Victor Lim, Claudia H.T. Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M. Raffield, Bram P. Prins, Aude Nicolas, Lisa R. Yanek, Guanjie Chen, Jennifer A. Brody, Edmond K. 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 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

Nature · 2024

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Summary

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.

Source type
Peer-reviewed study
DOI
10.1038/s41586-024-07019-6
Catalogue ID
SNmoj1y44j-y48v8j
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