Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries

作者：Alicia Huerta‐Chagoya, Joohyun Kim, Ravi Mandla, Yingchang Lu, Ken Suzuki, Lauren E. Petty, Hong Kiat Ng, Jaewon Choi, Simon Lee, Madhusmita Rout, Kuang Lin, Katherine Taylor, Carlos A. Aguilar‐Salinas, Lourdes García‐García, Clicerio González‐Villalpando, Christopher A. Haiman, Young Jin Kim, Soo Heon Kwak, Aaron Leong, Ruth J. F. Loos, Andrés Moreno‐Estrada, Andrew P. Morris, Lorena Orozco, Jerome I. Rotter, Dharambir K. Sanghera, Teresa Tusié‐Luna, Benjamin F. Voight, Marijana Vujković, Robin Walters, Tian Ge, Alisa K Manning, Marie Loh, Jennifer E. Below, Xueling Sim, Josep M. Mercader, Maggie C. Y. Ng, Linda S. Adair, Adebowale Adeyemo, Habibul Ahsan, Masato Akiyama, Ping An, Sonia S. Anand, Diane M. Becker, Alain G. Bertoni, Zheng Bian, Lawrence F. Bielak, John Blangero, Michael Boehnke, Erwin P. Böttinger, Donald W. Bowden, Fiona Bragg, Jennifer A. Brody, Thomas A. Buchanan, Brian E. Cade, Jin Fang Chai, John C. Chambers, Giriraj R. Chandak, Li-Ching Chang, Kyong‐Mi Chang, Miao-Li Chee, Chien-Hsiun Chen, Yuan-Tsong Chen, Zhengming Chen, Yii‐Der Ida Chen, Jihua Chen, Guanjie Chen, Shyh‐Huei Chen, Wei‐Min Chen, Ching‐Yu Cheng, Yoon Shin Cho, Hyeok Sun Choi, Lee‐Ming Chuang, Miguel Cruz, Mary Cushman, Swapan K. Das, Ralph A. DeFronzo, H Janaka deSilva, Latchezar Dimitrov, Ayo P. Doumatey, Shufa Du, Qing Duan, Ravindranath Duggirala, Leslie S. Emery, James C. Engert, Daniel S. Evans, Michele K. Evans, Sarah Finer, José C. Florez, James S. Floyd, Myriam Fornage, Eitan Frankel, Barry I. Freedman, Pauline Genter, Hertzel C. Gerstein, Mark O. Goodarzi, Penny Gordon‐Larsen, Mariaelisa Graff, Myron Gross, Yu Guo, Xiuqing Guo, Yang Hai, Craig L. Hanis, M. Geoffrey Hayes, Momoko Horikoshi, Annie-Green Howard, Sarah Hsu, Willa A. Hsueh, Wei Huang, Mengna Huang, Yi‐Jen Hung, Mi Yeong Hwang, Chii‐Min Hwu, Sahoko Ichihara, Michiya Igase, Eli Ipp, Mohammad Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Jost B. Jonas, Yoonjung Yoonie Joo, Edmond K. Kabagambe, Takashi Kadowaki, Yoichiro Kamatani, Fouad Kandeel, Sharon L. R. Kardia, Elizabeth W. Karlson, Anuradhani Kasturiratne, Norihiro Kato, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M. Keaton, Abel Kho, Chiea Chuen Khor, Muhammad G. Kibriya, Bong-Jo Kim, Woon-Puay Koh, Katsuhiko Kohara, Jaspal S. Kooner, Charles Kooperberg, Raymond J. Kreienkamp, Amel Lamri, Leslie A. Lange, Nanette R. Lee, Myung‐Shik Lee, Jung‐Jin Lee, Donna M. Lehman, Liming Li, Yun Li, Victor JY Lim, Jianjun Liu, Yongmei Liu, Simin Liu, Jirong Long, Tin Louie, Xi Luo, Jun Lv, Julie A. Lynch, Shiro Maeda, Anubha Mahajan, Nisa M. Maruthur, Fumihiko Matsuda, Mark I. McCarthy, Roberta McKean‐Cowdin, James B. Meigs, Iona Y. Millwood, Karen L. Mohlke, Ayesha A. Motala, Girish N. Nadkarni, Jerry L. Nadler, Masahiro Nakatochi, Mike A. Nalls, Uma Nayak, Aude Nicolas, Kari E. North, Darryl Nousome, Yukinori Okada, Sumit Paliwal, Ian Pan, James S. Pankow, Guillaume Paré, Jae‐Hyun Park, Kyong Soo Park, Esteban J. Parra, Sanjay R. Patel, Mark A. Pereira, Patricia A. Peyser, Fraser Pirie, Michael Preuß, Michael A. Province, Bruce M. Psaty, PSKDB PunyaSri, Leslie J. Raffel, Laura M. Raffield, Laura J. Rasmussen‐Torvik, Susan Redline, Alexander P. Reiner, Stephen S. Rich, Rebecca Rohde, Kathryn Roll, Rashedeh Roshani, Charles N. Rotimi, Charumathi Sabanayagam, Danish Saleheen, Kevin Sandow, Claudia Schurmann, Mohammad Shahriar, Douglas M. Shaw, Wayne Huey‐Herng Sheu, Jinxiu Shi, Xiao-Ou Shu, Megan M. Shuey, Moneeza K. Siddiqui, Jennifer A. Smith, Tamar Sofer, Cassandra N. Spracklen, Adrienne M. Stilp, Meng Sun, Yasuharu Tabara, E Shyong Tai, Salman M. Tajuddin, Atsushi Takahashi, Fumihiko Takeuchi, Jingyi Tan, Kent D. Taylor, Farook Thameem, Lin Tong, Fuu‐Jen Tsai, Philip S. Tsao, Miriam S. Udler, Adán Valladares‐Salgado, David A. van Heel, Rob M. vanDam, Rohit Varma, Maheak Vora, Niels H. Wacher, Ya Xing Wang, Ellie Wheeler, Eric A. Whitsel, Ananda R. Wickremasinghe, Genevieve L. Wojcik, Tien Yin Wong, Jer‐Yuarn Wu, Yong-Bing Xiang, Anny H. Xiang, Chittaranjan S. Yajnik, Ken Yamamoto, Toshimasa Yamauchi, Lisa R. Yanek, Jie Yao, Mitsuhiro Yokota, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Eleftheria Zeggini, Liang Zhang, Weihua Zhang, Wei Zheng, Alan B. Zonderman · 发表于：The Lancet Diabetes & Endocrinology · 年份：2026 · DOI：10.1016/s2213-8587(25)00405-x · 被引用次数：3 · 研究领域：Genetic Associations and Epidemiology、BRCA gene mutations in cancer、Genomics and Rare Diseases

BACKGROUND: Polygenic risk scores (PRSs) improve prediction of the development of type 2 diabetes over the use of clinical risk factors alone; however, they perform poorly in populations of non-European ancestry, limiting their global clinical utility. We aimed to deliver comprehensive and rigorously tested multi-ancestry PRSs for prediction in type 2 diabetes. METHODS: We conducted meta-analyses using data from type 2 diabetes genome-wide association studies (GWAS) across cohorts from five major global ancestries: European, African or African American, Admixed American, South Asian, and East Asian. We used summary statistics from the GWAS to construct single-ancestry PRSs (using the continuous-shrinkage PRS-CS method) and multi-ancestry PRSs (using the PRS-CSx method), and constructed ancestry-specific linkage disequilibrium panels to model pairwise correlations between single-nucleotide polymorphisms in GWAS during PRS construction. Models were validated for association with type 2 diabetes in at least four independent cohorts per ancestry. The effect sizes of PRSs were estimated as the odds ratio (OR) per SD of the PRS, and ORs for individuals at the 90th, 95th, and 97·5th PRS percentiles were compared with the IQR as a reference. We also tested our PRS models for prediction of diabetes incidence with or without additional clinical factors, as well as microvascular complications and comorbidities. FINDINGS: Our analysis used data from 409 959 individuals with type 2 diabet...