Multi-ancestry polygenic risk scores for the prediction of type 2 diabetes and complications in diverse ancestries.
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Huerta-Chagoya Alicia, Kim Joohyun, Mandla Ravi, Lu Yingchang, Suzuki Ken, Petty Lauren E, Ng Hong Kiat, Choi Jaewon, Lee Simon, Rout Madhusmita, Lin Kuang, Adair Linda S, Adeyemo Adebowale, Ahsan Habibul, Akiyama Masato, An Ping, Anand Sonia S, Becker Diane M, Bertoni Alain G, Bian Zheng, Bielak Lawrence F, Blangero John, Boehnke Michael, Bottinger Erwin P, Bowden Donald W, Bragg Fiona, Brody Jennifer A, Buchanan Thomas A, Cade Brian E, Chai Jin-Fang, Chambers John C, Chandak Giriraj R, Chang Li-Ching, Chang Kyong-Mi, Chee Miao-Li, Chen Chien-Hsiun, Chen Yuan-Tsong, Chen Zhengming, Chen Yii-Der I, Chen Ji, Chen Guanjie, Chen Shyh-Huei, Chen Wei-Min, Cheng Ching-Yu, Cho Yoon Shin, Choi Hyeok Sun, Chuang Lee-Ming, Cruz Miguel, Cushman Mary, Das Swapan K, DeFronzo Ralph A, deSilva H Janaka, Dimitrov Latchezar, Doumatey Ayo P, Du Shufa, Duan Qing, Duggirala Ravindranath, Emery Leslie S, Engert James C, Evans Daniel S, Evans Michele K, Finer Sarah, Florez Jose C, Floyd James S, Fornage Myriam, Frankel Elizabeth G, Freedman Barry I, García-García Lourdes, Genter Pauline, Gerstein Hertzel C, Goodarzi Mark O, Gordon-Larsen Penny, Graff Mariaelisa, Gross Myron, Guo Yu, Guo Xiuqing, Hai Yang, Hanis Craig L, Hayes MGeoffrey, Horikoshi Momoko, Howard Annie-Green, Hsu Sarah, Hsueh Willa, Huang Wei, Huang Mengna, Hung Yi-Jen, Hwang Mi Yeong, Hwu Chii-Min, Ichihara Sahoko, Igase Michiya, Ipp Eli, Islam Mohammad T, Isono Masato, Jang Hye-Mi, Jasmine Farzana, Jonas Jost B, Joo Yoonjung Y, Kabagambe Edmond, Kadowaki Takashi, Kamatani Yoichiro, Kandeel Fouad R, Kardia Sharon L R, Karlson Elizabeth W, Kasturiratne Anuradhani, Kato Norihiro, Katsuya Tomohiro, Kaur Varinderpal, Kawaguchi Takahisa, Keaton Jacob M, Kho Abel N, Khor Chiea-Chuen, Kibriya Muhammad, Kim Bong-Jo, Koh Woon-Puay, Kohara Katsuhiko, Kooner Jaspal S, Kooperberg Charles, Kreienkamp Raymond J, Lamri Amel, Lange Leslie A, Lee Nanette R, Lee Myung-Shik, Lee Jung-Jin, Lehman Donna M, Li Liming, Li Yun, Lim Victor Jy, Liu Jianjun, Liu Yongmei, Liu Simin, Long Jirong, Louie Tin, Luo Xi, Lv Jun, Lynch Julie A, Maeda Shiro, Mahajan Anubha, Maruthur Nisa M, Matsuda Fumihiko, McCarthy Mark I, McKean-Cowdin Roberta, Meigs James B, Millwood Iona Y, Mohlke Karen L, Motala Ayesha A, Nadkarni Girish N, Nadler Jerry L, Nakatochi Masahiro, Nalls Mike A, Nayak Uma, Nicolas Aude, North Kari E, Nousome Darryl, Okada Yukinori, Pan Ian, Pankow James S, Paré Guillaume, Park Jaehyun, Park Kyong Soo, Parra Esteban J, Patel Sanjay R, Pereira Mark A, Peyser Patricia A, Pirie Fraser J, Preuss Michael, Province Michael A, Psaty Bruce M, Raffel Leslie J, Raffield Laura M, Rasmussen-Torvik Laura J, Redline Susan, Reiner Alexander P, Rich Stephen S, Rohde Rebecca, Roll Kathryn, Roshani Rashedeh, Rotimi Charles N, Sabanayagam Charumathi, Saleheen Danish, Sandow Kevin, Schurmann Claudia, Shahriar Mohammad, Shaw Douglas M, Sheu Wayne H-H, Shi Jinxiu, Shu Xiao-Ou, Shuey Megan M, Siddiqui Moneeza K, Smith Jennifer A, Sofer Tamar, Spracklen Cassandra N, Stilp Adrienne M, Sun Meng, Tabara Yasuharu, Tai E-Shyong, Tajuddin Salman M, Takahashi Atsushi, Takeuchi Fumihiko, Tan Jingyi, Taylor Kent D, Taylor Katherine, Thameem Farook, Tong Lin, Tsai Fuu-Jen, Tsao Philip S, Udler Miriam S, Valladares-Salgado Adan, van Heel David A, vanDam Rob M, Varma Rohit, Vora Maheak, Wacher-Rodarte Niels, Wang Ya-Xing, Wheeler Ellie, Whitsel Eric A, Wickremasinghe Ananda R, Wojcik Genevieve L, Wong Tien Y, Wu Jer-Yuarn, Xiang Yong-Bing, Xiang Anny H, Yajnik Chittaranjan S, Yamamoto Ken, Yamauchi Toshimasa, Yanek Lisa R, Yao Jie, Yokota Mitsuhiro, Yu Canqing, Yuan Jian-Min, Yusuf Salim, Zeggini Eleftheria, Zhang Liang, Zhang Weihua, Zheng Wei, Zonderman Alan B, ENSA Genomics Consortium, Genes & Health Research Team, VA Million Veteran Program, Aguilar-Salinas Carlos A, González-Villalpando Clicerio, Haiman Christopher A, Kim Young Jin, Kwak Soo Heon, Leong Aaron, Loos Ruth J F, Moreno-Estrada Andres, Morris Andrew P, Orozco Lorena, Rotter Jerome I, Sanghera Dharambir, Tusie-Luna Teresa, Voight Benjamin F, Vujkovic Marijana, Walters Robin G, Ge Tian, Manning Alisa K, Loh Marie, Below Jennifer E, Sim Xueling, Mercader Josep M, Ng Maggie C Y, D-PRISM Consortium
Аннотация
METHODS: We conducted the largest global effort to date to harmonize T2D genome-wide association study (GWAS) meta-analyses across five ancestries-European (EUR), African/African American (AFR), Admixed American (AMR), South Asian (SAS), and East Asian (EAS)-including 360,000 T2D cases and 1·8 million controls (41% non-EUR). We constructed ancestry-specific and multi-ancestry PRSs in training datasets including 11,000 T2D cases and 32,000 controls, and validated their performance in independent datasets including 39,000 T2D cases and 126,000 controls of diverse ancestries. In the All of Us Research Program, we compared these PRSs to those from the Polygenic Score Catalog and assessed their ability to predict diabetes micro- and macrovascular complications.
FINDINGS: Ancestry-specific PRSs showed limited prediction power for T2D in AFR, AMR, and SAS compared to EUR and EAS. In contrast, multi-ancestry PRSs, built using GWAS data from five ancestries, substantially improved T2D prediction across all ancestries. Compared to those in the interquartile range, individuals at the 97·5th percentile of their PRSs had a 6-fold increased T2D risk in AMR, EAS, and EUR, and ≥3-fold in AFR and SAS. These PRSs were also associated with the development of microvascular complications and outperformed all previously reported PRSs for all ancestries.
INTERPRETATION: We developed and extensively validated the most up-to-date T2D PRSs across diverse ancestry groups. These PRSs are publicly available to support further evaluation of their clinical utility in diverse ancestries.