This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

[Preprint]. 2025 Jul 23:2025.07.21.25331778.

doi: 10.1101/2025.07.21.25331778.

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

Alicia Huerta-Chagoya^{1

2

3

4}, Joohyun Kim⁵, Ravi Mandla^{1

2

3}, Yingchang Lu⁵, Ken Suzuki^{6

7

8}, Lauren E Petty⁵, Hong Kiat Ng⁹, Jaewon Choi¹⁰, Simon Lee¹¹, Madhusmita Rout¹², Kuang Lin¹³, Linda S Adair¹⁴, Adebowale Adeyemo¹⁵, Habibul Ahsan¹⁶, Masato Akiyama^{17

18}, Ping An¹⁹, Sonia S Anand^{20

21

22}, Diane M Becker²³, Alain G Bertoni²⁴, Zheng Bian²⁵, Lawrence F Bielak²⁶, John Blangero²⁷, Michael Boehnke²⁸, Erwin P Bottinger^{29

30

11}, Donald W Bowden^{31

32

33}, Fiona Bragg^{13

34}, Jennifer A Brody³⁵, Thomas A Buchanan³⁶, Brian E Cade^{37

38}, Jin-Fang Chai³⁹, John C Chambers⁹, Giriraj R Chandak^{40

41}, Li-Ching Chang⁴², Kyong-Mi Chang^{43

44}, Miao-Li Chee⁴⁵, Chien-Hsiun Chen⁴², Yuan-Tsong Chen⁴², Zhengming Chen¹³, Yii-Der I Chen⁴⁶, Ji Chen⁴⁷, Guanjie Chen¹⁵, Shyh-Huei Chen⁴⁸, Wei-Min Chen⁴⁹, Ching-Yu Cheng^{50

51

45

52}, Yoon Shin Cho⁵³, Hyeok Sun Choi⁵³, Lee-Ming Chuang^{54

55}, Miguel Cruz⁵⁶, Mary Cushman⁵⁷, Swapan K Das⁵⁸, Ralph A DeFronzo⁵⁹, H Janaka deSilva⁶⁰, Latchezar Dimitrov³², Ayo P Doumatey¹⁵, Shufa Du¹⁴, Qing Duan⁶¹, Ravindranath Duggirala²⁷, Leslie S Emery⁶², James C Engert⁶³, Daniel S Evans⁶⁴, Michele K Evans⁶⁵, Sarah Finer⁶⁶, Jose C Florez^{1

4

67}, James S Floyd³⁵, Myriam Fornage⁶⁸, Elizabeth G Frankel⁵, Barry I Freedman⁶⁹, Lourdes García-García⁷⁰, Pauline Genter⁷¹, Hertzel C Gerstein^{20

21

22}, Mark O Goodarzi⁷², Penny Gordon-Larsen¹⁴, Mariaelisa Graff⁷³, Myron Gross⁷⁴, Yu Guo²⁵, Xiuqing Guo⁴⁶, Yang Hai⁴⁶, Craig L Hanis⁷⁵, MGeoffrey Hayes^{76

77

78}, Momoko Horikoshi⁷⁹, Annie-Green Howard⁸⁰, Sarah Hsu^{1

3}, Willa Hsueh⁸¹, Wei Huang⁸², Mengna Huang^{83

84}, Yi-Jen Hung^{85

86}, Mi Yeong Hwang⁸⁷, Chii-Min Hwu^{88

89}, Sahoko Ichihara⁹⁰, Michiya Igase⁹¹, Eli Ipp⁷¹, Mohammad T Islam⁹², Masato Isono⁹³, Hye-Mi Jang⁸⁷, Farzana Jasmine¹⁶, Jost B Jonas^{94

95

96

97

98}, Yoonjung Y Joo^{99

78}, Edmond Kabagambe¹⁰⁰, Takashi Kadowaki⁷, Yoichiro Kamatani^{101

102}, Fouad R Kandeel¹⁰³, Sharon L R Kardia²⁶, Elizabeth W Karlson¹⁰⁴, Anuradhani Kasturiratne¹⁰⁵, Norihiro Kato⁹³, Tomohiro Katsuya^{106

107}, Varinderpal Kaur^{1

2

3}, Takahisa Kawaguchi¹⁰⁸, Jacob M Keaton^{32

100}, Abel N Kho^{109

110}, Chiea-Chuen Khor^{111

45

112}, Muhammad Kibriya¹⁶, Bong-Jo Kim⁸⁷, Woon-Puay Koh^{113

39}, Katsuhiko Kohara¹¹⁴, Jaspal S Kooner¹¹⁵, Charles Kooperberg¹¹⁶, Raymond J Kreienkamp^{1

4

2

117}, Amel Lamri^{20

21}, Leslie A Lange¹¹⁸, Nanette R Lee¹¹⁹, Myung-Shik Lee^{120

121}, Jung-Jin Lee¹²², Donna M Lehman⁵⁹, Liming Li¹²³, Yun Li¹²⁴, Victor Jy Lim³⁹, Jianjun Liu^{111

125}, Yongmei Liu^{126

24}, Simin Liu^{127

128

129

130}, Jirong Long¹⁰⁰, Tin Louie⁶², Xi Luo¹³¹, Jun Lv¹²³, Julie A Lynch^{132

133}, Shiro Maeda^{79

134

135}, Anubha Mahajan¹³⁶, Nisa M Maruthur¹³⁷, Fumihiko Matsuda¹⁰⁸, Mark I McCarthy^{136

138

139}, Roberta McKean-Cowdin¹⁴⁰, James B Meigs^{1

4

141}, Iona Y Millwood¹³, Karen L Mohlke⁶¹, Ayesha A Motala¹⁴², Girish N Nadkarni^{11

29}, Jerry L Nadler¹⁴³, Masahiro Nakatochi¹⁴⁴, Mike A Nalls^{145

146

147}, Uma Nayak¹⁴⁸, Aude Nicolas¹⁴⁵, Kari E North⁷³, Darryl Nousome¹⁴⁰, Yukinori Okada^{149

150

151}, Ian Pan⁸⁴, James S Pankow¹⁵², Guillaume Paré^{153

21

22}, Jaehyun Park⁵, Kyong Soo Park^{154

155}, Esteban J Parra¹⁵⁶, Sanjay R Patel¹⁵⁷, Mark A Pereira¹⁵², Patricia A Peyser²⁶, Fraser J Pirie¹⁴², Michael Preuss¹¹, Michael A Province¹⁹, Bruce M Psaty¹⁵⁸, Leslie J Raffel¹⁵⁹, Laura M Raffield⁶¹, Laura J Rasmussen-Torvik¹⁶⁰, Susan Redline^{161

37

38}, Alexander P Reiner^{162

116}, Stephen S Rich¹⁶³, Rebecca Rohde⁷³, Kathryn Roll⁴⁶, Rashedeh Roshani⁵, Charles N Rotimi¹⁵, Charumathi Sabanayagam^{45

50}, Danish Saleheen⁴³, Kevin Sandow⁴⁶, Claudia Schurmann^{29

30

11}, Mohammad Shahriar¹⁶, Douglas M Shaw⁵, Wayne H-H Sheu^{86

88

89

164

165}, Jinxiu Shi⁸², Xiao-Ou Shu¹⁰⁰, Megan M Shuey⁵, Moneeza K Siddiqui⁶⁶, Jennifer A Smith^{26

166}, Tamar Sofer^{167

168

4}, Cassandra N Spracklen^{61

169}, Adrienne M Stilp⁶², Meng Sun¹⁷⁰, Yasuharu Tabara¹⁰⁸, E-Shyong Tai^{125

39

112}, Salman M Tajuddin⁶⁵, Atsushi Takahashi^{101

171}, Fumihiko Takeuchi⁹³, Jingyi Tan⁴⁶, Kent D Taylor⁴⁶, Katherine Taylor¹, Farook Thameem¹⁷², Lin Tong¹⁶, Fuu-Jen Tsai¹⁷³, Philip S Tsao^{174

175}, Miriam S Udler^{1

4

2

3}, Adan Valladares-Salgado⁵⁶, David A van Heel¹⁷⁶, Rob M vanDam^{39

125}, Rohit Varma¹⁷⁷, Maheak Vora^{1

2}, Niels Wacher-Rodarte¹⁷⁸, Ya-Xing Wang¹⁷⁹, Ellie Wheeler^{180

47}, Eric A Whitsel^{73

181}, Ananda R Wickremasinghe¹⁰⁵, Genevieve L Wojcik¹⁸², Tien Y Wong^{45

50

51}, Jer-Yuarn Wu⁴², Yong-Bing Xiang^{183

184}, Anny H Xiang¹⁸⁵, Chittaranjan S Yajnik¹⁸⁶, Ken Yamamoto¹⁸⁷, Toshimasa Yamauchi⁷, Lisa R Yanek²³, Jie Yao⁴⁶, Mitsuhiro Yokota¹⁸⁷, Canqing Yu¹²³, Jian-Min Yuan^{188

189}, Salim Yusuf^{190

21

22}, Eleftheria Zeggini^{191

192}, Liang Zhang⁴⁵, Weihua Zhang¹⁹³, Wei Zheng¹⁹⁴, Alan B Zonderman⁶⁵; ENSA Genomics Consortium; Genes & Health Research Team; VA Million Veteran Program; Carlos A Aguilar-Salinas^{195

196}, Clicerio González-Villalpando¹⁹⁷, Christopher A Haiman¹⁹⁸, Young Jin Kim⁸⁷, Soo Heon Kwak¹⁵⁴, Aaron Leong^{1

2

199

3

141

200}, Ruth J F Loos^{11

201}, Andres Moreno-Estrada²⁰², Andrew P Morris^{8

203}, Lorena Orozco²⁰⁴, Jerome I Rotter⁴⁶, Dharambir Sanghera¹², Teresa Tusie-Luna²⁰⁵, Benjamin F Voight^{206

207

208

209}, Marijana Vujkovic^{210

206}, Robin G Walters¹³, Tian Ge²¹¹, Alisa K Manning^{212

1

4}, Marie Loh^{9

213

214}, Jennifer E Below⁵, Xueling Sim³⁹, Josep M Mercader^{1

4

2

3

215}, Maggie C Y Ng⁵; D-PRISM Consortium

Affiliations

¹ Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 2142, USA.
² Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
³ Diabetes Unit, Massachusetts General Hospital, Boston, MA, 2114, USA.
⁴ Department of Medicine, Harvard Medical School, Boston, MA, 2215, USA.
⁵ Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Statistical Genetics, Osaka University, Osaka, 565-0871, Japan.
⁷ Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan.
⁸ Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK.
⁹ Lee Kong Chian School of Medicine, Clinical Sciences Building, Nanyang Technological University, Singapore, 308232, Singapore.
¹⁰ Department of Internal Medicine, Seoul National University Hospital, Seoul, 3080, South Korea.
¹¹ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Department of Pediatrics, Section of Genetics, University of Oklahoma, Oklahoma, OK, USA.
¹³ Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
¹⁴ Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
¹⁵ Center for Research on Genomics and Global Health, National Human Genome Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁶ Biological Sciences Division, Public Health Sciences, The University of Chicago, Chicago, IL, 60637, USA.
¹⁷ Laboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁸ Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
¹⁹ Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA.
²⁰ Department of Medicine, McMaster University, Hamilton, ON, Canada.
²¹ Population Health Research Institute, Hamilton, ON, Canada.
²² Hamilton Health Sciences, Hamilton, ON, Canada.
²³ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
²⁴ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
²⁵ Chinese Academy of Medical Sciences, Beijing, 100730, China.
²⁶ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
²⁷ Human Genetics and STDOI, University of Texas Rio Grande Valley, Edinburg, TX, USA.
²⁸ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
²⁹ Digital Health Center, Digitl Engineering Faculty of Hasso Plattner Institue and University Potsdam, Potsdam, Germany.
³⁰ Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³¹ Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³² Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³³ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³⁴ Health Data Research UK Oxford, University of Oxford, Oxford, UK.
³⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
³⁶ Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³⁷ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
³⁸ Harvard Medical School, Boston, MA, USA.
³⁹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
⁴⁰ Genomic Research on Complex diseases, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India.
⁴¹ Lightening Lives, Hyderabad, India.
⁴² Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
⁴³ Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴⁴ Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴⁵ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore.
⁴⁶ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁴⁷ Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
⁴⁸ Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
⁴⁹ Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁵⁰ Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
⁵¹ Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, 119228, Singapore.
⁵² Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
⁵³ Biomedical Science, Hallym University, Chuncheon, 24252, South Korea.
⁵⁴ Department of Internal Medicine, Division of Endocrinology and Metabolism, National Taiwan University Hospital, Taipei, Taiwan.
⁵⁵ College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵⁶ Unidad de Investigación Médica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
⁵⁷ Department of Medicine, University of Vermont, Colchester, VT, USA.
⁵⁸ Department of Internal Medicine, Section on Endocrinology and Metabolism, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁵⁹ Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁶⁰ Department of Medicine, Faculty of Medicine, University of Kelaniya, Sri Lanka.
⁶¹ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁶² Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁶³ Department of Medicine, McGill University, Montreal, QC, Canada.
⁶⁴ California Pacific Medical Center Research Institute, San Francisco, CA, USA.
⁶⁵ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
⁶⁶ Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
⁶⁷ Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
⁶⁸ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁶⁹ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁷⁰ Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
⁷¹ Division of Endocrinology & Metabolism, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁷² Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷³ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷⁴ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55454, USA.
⁷⁵ Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁷⁶ Department of Anthropology, Northwestern University, Evanston, IL, USA.
⁷⁷ Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁷⁸ Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁷⁹ Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
⁸⁰ Department of Biostatistics, Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁸¹ Department of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁸² Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT), Shanghai, 200032, China.
⁸³ Center for Global Cardiometabolic Health, Brown University, Providence, RI, USA.
⁸⁴ Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.
⁸⁵ Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan.
⁸⁶ School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁸⁷ Department of Precision Medicine, Division of Genome Science, National Institute of Health, Chungcheongbuk-do, 28159, Republic of Korea.
⁸⁸ Department of Medicine, Section of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸⁹ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁹⁰ Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, 329-0498, Japan.
⁹¹ Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Ehime, 791-0295, Japan.
⁹² U Chicago Research, Uttara, Dhaka, 1230, Bangladesh.
⁹³ Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
⁹⁴ Rothschild Foundation Hospital, Paris, France.
⁹⁵ Singapore Eye Research Institute, Singapore National Eye Center, Singapore.
⁹⁶ Privatpraxis Prof Jonas und Dr. Panda-Jonas, Heidelberg, Germany.
⁹⁷ Beijing Visual Science and Translational Eye Research Institute (BERI), Beijing Tsinghua Changgung Hospital, Tsinghua Medicine, Tsinghua University, Beijing, China.
⁹⁸ L V Prasad Eye Institute, Hyderabad, Telangana, India.
⁹⁹ Department of Health and Biomedical Informatics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁰⁰ Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰¹ Laboratory for Statistical and Translational Genetics, RIKEN Centre for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁰² Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
¹⁰³ Departments of Clinical Diabetes, Endocrinology & Metabolism and Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA, USA.
¹⁰⁴ Department of Medicine, Brigham and Women's Hospital, Boston, MA, 2215, USA.
¹⁰⁵ Department of Public Health, Faculty of Medicine, University of Kelaniya, Sri Lanka.
¹⁰⁶ Department of Clinical Gene Therapy, Osaka University, Osaka, 565-0871, Japan.
¹⁰⁷ Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
¹⁰⁸ Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
¹⁰⁹ Center for Health Information Partnerships, Institute for Public Health and Medicine, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USA.
¹¹⁰ Department of Medicine, Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹¹ Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, 138672, Singapore.
¹¹² Duke-NUS Medical School, Singapore, 169857, Singapore.
¹¹³ Health Services and Systems Research, Duke-NUS Medical School, Singapore, 169857, Singapore.
¹¹⁴ Department of Regional Resource Management, Ehime University Faculty of Collaborative Regional Innovation, Ehime, 790-8577, Japan.
¹¹⁵ Department of Cardiology, Ealing Hosptial, London North West Healthcare NHS Trust, Middlesex, UB1 3HW, UK.
¹¹⁶ Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹¹⁷ Department of Pediatrics, Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
¹¹⁸ Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
¹¹⁹ Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, 6000, Philippines.
¹²⁰ Severance Biomedical Science Institute and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 3722, South Korea.
¹²¹ Soonchunhyang Institute of Medi-bio Science, Cheonan, 31151, South Korea.
¹²² Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹²³ Department of Epidemiology and Biostatistics, Peking University Health Science Centre, Beijing, 100191, China.
¹²⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹²⁵ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
¹²⁶ Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
¹²⁷ Department of Epidemiology and Biostatistics, The Joe Wen School of Population & Pubic Health, UCI, Irvine, CA, USA.
¹²⁸ Center for Global Cardiometabolic Health and Nutrition, the University of California, Irvine (UCI), Irvine, CA, USA.
¹²⁹ Division of Cardiology, Department of Medicine, School of Medicine, UCI, USA.
¹³⁰ Center for Global Cardiometabolic Health, Brown University School of Public Health, Providence, RI, USA.
¹³¹ Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹³² Salt Lake City VA Medical Center, Salt Lake City, UT, USA.
¹³³ University of Utah, School of Medicine, Salt Lake City, UT, USA.
¹³⁴ Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0213, Japan.
¹³⁵ Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Okinawa, 903-0213, Japan.
¹³⁶ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
¹³⁷ Department of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹³⁸ Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
¹³⁹ Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
¹⁴⁰ Department of Preventative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
¹⁴¹ Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
¹⁴² Department of Diabetes and Endocrinology, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁴³ Department of Medicine and Endocrinology Division, University of California Davis School of Medicine, Sacramento, CA, USA.
¹⁴⁴ Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, 461-8673, Japan.
¹⁴⁵ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
¹⁴⁶ Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
¹⁴⁷ DataTecnica LLC, Washington, DC, USA.
¹⁴⁸ Department of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹⁴⁹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Tokyo, 565-0871, Japan.
¹⁵⁰ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, 565-0871, Japan.
¹⁵¹ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁵² Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
¹⁵³ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
¹⁵⁴ Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, 3080, South Korea.
¹⁵⁵ Department of Internal Medicine, Konkuk University Medical Center, Seoul, 3080, South Korea.
¹⁵⁶ Department of Anthropology, University of Toronto at Mississauga, Mississauga, Canada.
¹⁵⁷ Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁵⁸ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, USA.
¹⁵⁹ Department of Pediatrics, Division of Genetic and Genomic Medicine, UCI Irvine School of Medicine, Irvine, CA, USA.
¹⁶⁰ Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
¹⁶¹ Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁶² Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁶³ Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
¹⁶⁴ Department of Medicine, Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁶⁵ Institutes of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan.
¹⁶⁶ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
¹⁶⁷ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁶⁸ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁶⁹ Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, 1003, USA.
¹⁷⁰ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 9DU, UK.
¹⁷¹ Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Osaka, 565-8565, Japan.
¹⁷² Department of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University, Safat, Kuwait.
¹⁷³ Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan.
¹⁷⁴ Department of Medicine, Stanford University, Palo Alto, CA, USA.
¹⁷⁵ VA Palo Alto Health Care System, Palo Alto, CA, USA.
¹⁷⁶ Blizard Institute, Queen Mary University of London, London, UK.
¹⁷⁷ Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center, Los Angeles, CA, USA.
¹⁷⁸ Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
¹⁷⁹ Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, 100005, China.
¹⁸⁰ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
¹⁸¹ Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁸² Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
¹⁸³ State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
¹⁸⁴ Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
¹⁸⁵ Department of Research & Evaluation, Division of Biostatistics Research, Kaiser Permanente of Southern California, Pasadena, CA, USA.
¹⁸⁶ Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India.
¹⁸⁷ Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, 830-0011, Japan.
¹⁸⁸ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, 15232, USA.
¹⁸⁹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15232, USA.
¹⁹⁰ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁹¹ Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
¹⁹² Technical University of Munich (TUM), TUM University Hospital, TUM School of Medicine and Health, Munich, 81675, Germany.
¹⁹³ Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
¹⁹⁴ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37203, USA.
¹⁹⁵ Unidad de Investigación de Enfermedades Metabólicas, Research Direction of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
¹⁹⁶ Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico.
¹⁹⁷ Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Mexico.
¹⁹⁸ Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, CA, USA.
¹⁹⁹ Department of Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
²⁰⁰ Endocrine Division, Massachusetts General Hospital, Boston, MA, 2114, USA.
²⁰¹ The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁰² Aging Research Center, Cinvestav Sede Sur, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico.
²⁰³ NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
²⁰⁴ Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
²⁰⁵ Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
²⁰⁶ Corporal Michael J. Crescenz Philadelphia VA Medical Center, Philadelphia, PA, USA.
²⁰⁷ Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
²⁰⁸ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
²⁰⁹ Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
²¹⁰ Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
²¹¹ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
²¹² Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, 2114, USA.
²¹³ Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, UK.
²¹⁴ Research Division, National Skin Centre, Singapore.
²¹⁵ Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

PMID: 40778152
PMCID: PMC12330429
DOI: 10.1101/2025.07.21.25331778

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

Alicia Huerta-Chagoya et al. medRxiv. 2025.

[Preprint]. 2025 Jul 23:2025.07.21.25331778.

doi: 10.1101/2025.07.21.25331778.

Authors

Affiliations

¹ Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, 2142, USA.
² Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
³ Diabetes Unit, Massachusetts General Hospital, Boston, MA, 2114, USA.
⁴ Department of Medicine, Harvard Medical School, Boston, MA, 2215, USA.
⁵ Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Department of Statistical Genetics, Osaka University, Osaka, 565-0871, Japan.
⁷ Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan.
⁸ Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, UK.
⁹ Lee Kong Chian School of Medicine, Clinical Sciences Building, Nanyang Technological University, Singapore, 308232, Singapore.
¹⁰ Department of Internal Medicine, Seoul National University Hospital, Seoul, 3080, South Korea.
¹¹ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Department of Pediatrics, Section of Genetics, University of Oklahoma, Oklahoma, OK, USA.
¹³ Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
¹⁴ Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
¹⁵ Center for Research on Genomics and Global Health, National Human Genome Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁶ Biological Sciences Division, Public Health Sciences, The University of Chicago, Chicago, IL, 60637, USA.
¹⁷ Laboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁸ Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
¹⁹ Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA.
²⁰ Department of Medicine, McMaster University, Hamilton, ON, Canada.
²¹ Population Health Research Institute, Hamilton, ON, Canada.
²² Hamilton Health Sciences, Hamilton, ON, Canada.
²³ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
²⁴ Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
²⁵ Chinese Academy of Medical Sciences, Beijing, 100730, China.
²⁶ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
²⁷ Human Genetics and STDOI, University of Texas Rio Grande Valley, Edinburg, TX, USA.
²⁸ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
²⁹ Digital Health Center, Digitl Engineering Faculty of Hasso Plattner Institue and University Potsdam, Potsdam, Germany.
³⁰ Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³¹ Center for Diabetes Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³² Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³³ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³⁴ Health Data Research UK Oxford, University of Oxford, Oxford, UK.
³⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
³⁶ Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³⁷ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
³⁸ Harvard Medical School, Boston, MA, USA.
³⁹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
⁴⁰ Genomic Research on Complex diseases, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India.
⁴¹ Lightening Lives, Hyderabad, India.
⁴² Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
⁴³ Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴⁴ Division of Translational Medicine and Human Genetics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴⁵ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 168751, Singapore.
⁴⁶ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁴⁷ Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
⁴⁸ Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA.
⁴⁹ Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁵⁰ Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
⁵¹ Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, 119228, Singapore.
⁵² Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
⁵³ Biomedical Science, Hallym University, Chuncheon, 24252, South Korea.
⁵⁴ Department of Internal Medicine, Division of Endocrinology and Metabolism, National Taiwan University Hospital, Taipei, Taiwan.
⁵⁵ College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵⁶ Unidad de Investigación Médica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
⁵⁷ Department of Medicine, University of Vermont, Colchester, VT, USA.
⁵⁸ Department of Internal Medicine, Section on Endocrinology and Metabolism, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁵⁹ Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁶⁰ Department of Medicine, Faculty of Medicine, University of Kelaniya, Sri Lanka.
⁶¹ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁶² Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁶³ Department of Medicine, McGill University, Montreal, QC, Canada.
⁶⁴ California Pacific Medical Center Research Institute, San Francisco, CA, USA.
⁶⁵ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
⁶⁶ Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
⁶⁷ Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
⁶⁸ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
⁶⁹ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁷⁰ Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
⁷¹ Division of Endocrinology & Metabolism, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁷² Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷³ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷⁴ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55454, USA.
⁷⁵ Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁷⁶ Department of Anthropology, Northwestern University, Evanston, IL, USA.
⁷⁷ Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁷⁸ Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁷⁹ Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
⁸⁰ Department of Biostatistics, Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
⁸¹ Department of Internal Medicine, Diabetes and Metabolism Research Center, Ohio State University Wexner Medical Center, Columbus, OH, USA.
⁸² Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT), Shanghai, 200032, China.
⁸³ Center for Global Cardiometabolic Health, Brown University, Providence, RI, USA.
⁸⁴ Department of Epidemiology, Brown University School of Public Health, Providence, RI, USA.
⁸⁵ Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan.
⁸⁶ School of Medicine, National Defense Medical Center, Taipei, Taiwan.
⁸⁷ Department of Precision Medicine, Division of Genome Science, National Institute of Health, Chungcheongbuk-do, 28159, Republic of Korea.
⁸⁸ Department of Medicine, Section of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸⁹ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
⁹⁰ Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, 329-0498, Japan.
⁹¹ Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Ehime, 791-0295, Japan.
⁹² U Chicago Research, Uttara, Dhaka, 1230, Bangladesh.
⁹³ Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.
⁹⁴ Rothschild Foundation Hospital, Paris, France.
⁹⁵ Singapore Eye Research Institute, Singapore National Eye Center, Singapore.
⁹⁶ Privatpraxis Prof Jonas und Dr. Panda-Jonas, Heidelberg, Germany.
⁹⁷ Beijing Visual Science and Translational Eye Research Institute (BERI), Beijing Tsinghua Changgung Hospital, Tsinghua Medicine, Tsinghua University, Beijing, China.
⁹⁸ L V Prasad Eye Institute, Hyderabad, Telangana, India.
⁹⁹ Department of Health and Biomedical Informatics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁰⁰ Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰¹ Laboratory for Statistical and Translational Genetics, RIKEN Centre for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁰² Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
¹⁰³ Departments of Clinical Diabetes, Endocrinology & Metabolism and Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA, USA.
¹⁰⁴ Department of Medicine, Brigham and Women's Hospital, Boston, MA, 2215, USA.
¹⁰⁵ Department of Public Health, Faculty of Medicine, University of Kelaniya, Sri Lanka.
¹⁰⁶ Department of Clinical Gene Therapy, Osaka University, Osaka, 565-0871, Japan.
¹⁰⁷ Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.
¹⁰⁸ Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8507, Japan.
¹⁰⁹ Center for Health Information Partnerships, Institute for Public Health and Medicine, Northwestern UniversityFeinberg School of Medicine, Chicago, IL, USA.
¹¹⁰ Department of Medicine, Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹¹¹ Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, 138672, Singapore.
¹¹² Duke-NUS Medical School, Singapore, 169857, Singapore.
¹¹³ Health Services and Systems Research, Duke-NUS Medical School, Singapore, 169857, Singapore.
¹¹⁴ Department of Regional Resource Management, Ehime University Faculty of Collaborative Regional Innovation, Ehime, 790-8577, Japan.
¹¹⁵ Department of Cardiology, Ealing Hosptial, London North West Healthcare NHS Trust, Middlesex, UB1 3HW, UK.
¹¹⁶ Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹¹⁷ Department of Pediatrics, Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.
¹¹⁸ Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
¹¹⁹ Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, 6000, Philippines.
¹²⁰ Severance Biomedical Science Institute and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 3722, South Korea.
¹²¹ Soonchunhyang Institute of Medi-bio Science, Cheonan, 31151, South Korea.
¹²² Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹²³ Department of Epidemiology and Biostatistics, Peking University Health Science Centre, Beijing, 100191, China.
¹²⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹²⁵ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, 117549, Singapore.
¹²⁶ Department of Medicine, Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
¹²⁷ Department of Epidemiology and Biostatistics, The Joe Wen School of Population & Pubic Health, UCI, Irvine, CA, USA.
¹²⁸ Center for Global Cardiometabolic Health and Nutrition, the University of California, Irvine (UCI), Irvine, CA, USA.
¹²⁹ Division of Cardiology, Department of Medicine, School of Medicine, UCI, USA.
¹³⁰ Center for Global Cardiometabolic Health, Brown University School of Public Health, Providence, RI, USA.
¹³¹ Department of Biostatistics and Data Science, University of Texas Health Science Center at Houston, Houston, TX, USA.
¹³² Salt Lake City VA Medical Center, Salt Lake City, UT, USA.
¹³³ University of Utah, School of Medicine, Salt Lake City, UT, USA.
¹³⁴ Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0213, Japan.
¹³⁵ Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Okinawa, 903-0213, Japan.
¹³⁶ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
¹³⁷ Department of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹³⁸ Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
¹³⁹ Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
¹⁴⁰ Department of Preventative Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
¹⁴¹ Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
¹⁴² Department of Diabetes and Endocrinology, Nelson R Mandela School of Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
¹⁴³ Department of Medicine and Endocrinology Division, University of California Davis School of Medicine, Sacramento, CA, USA.
¹⁴⁴ Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, 461-8673, Japan.
¹⁴⁵ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
¹⁴⁶ Center for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
¹⁴⁷ DataTecnica LLC, Washington, DC, USA.
¹⁴⁸ Department of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA.
¹⁴⁹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Tokyo, 565-0871, Japan.
¹⁵⁰ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, 565-0871, Japan.
¹⁵¹ Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁵² Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
¹⁵³ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
¹⁵⁴ Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, 3080, South Korea.
¹⁵⁵ Department of Internal Medicine, Konkuk University Medical Center, Seoul, 3080, South Korea.
¹⁵⁶ Department of Anthropology, University of Toronto at Mississauga, Mississauga, Canada.
¹⁵⁷ Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁵⁸ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, WA, USA.
¹⁵⁹ Department of Pediatrics, Division of Genetic and Genomic Medicine, UCI Irvine School of Medicine, Irvine, CA, USA.
¹⁶⁰ Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
¹⁶¹ Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁶² Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁶³ Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
¹⁶⁴ Department of Medicine, Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁶⁵ Institutes of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan.
¹⁶⁶ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
¹⁶⁷ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁶⁸ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁶⁹ Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, 1003, USA.
¹⁷⁰ Nuffield Department of Surgical Sciences, University of Oxford, Oxford, OX3 9DU, UK.
¹⁷¹ Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Osaka, 565-8565, Japan.
¹⁷² Department of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University, Safat, Kuwait.
¹⁷³ Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, 40402, Taiwan.
¹⁷⁴ Department of Medicine, Stanford University, Palo Alto, CA, USA.
¹⁷⁵ VA Palo Alto Health Care System, Palo Alto, CA, USA.
¹⁷⁶ Blizard Institute, Queen Mary University of London, London, UK.
¹⁷⁷ Southern California Eye Institute, CHA Hollywood Presbyterian Medical Center, Los Angeles, CA, USA.
¹⁷⁸ Unidad de Investigación Médica en Epidemiologia Clinica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico.
¹⁷⁹ Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, 100005, China.
¹⁸⁰ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
¹⁸¹ Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹⁸² Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
¹⁸³ State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
¹⁸⁴ Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China.
¹⁸⁵ Department of Research & Evaluation, Division of Biostatistics Research, Kaiser Permanente of Southern California, Pasadena, CA, USA.
¹⁸⁶ Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India.
¹⁸⁷ Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, 830-0011, Japan.
¹⁸⁸ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, 15232, USA.
¹⁸⁹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15232, USA.
¹⁹⁰ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁹¹ Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
¹⁹² Technical University of Munich (TUM), TUM University Hospital, TUM School of Medicine and Health, Munich, 81675, Germany.
¹⁹³ Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
¹⁹⁴ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37203, USA.
¹⁹⁵ Unidad de Investigación de Enfermedades Metabólicas, Research Direction of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
¹⁹⁶ Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico.
¹⁹⁷ Centro de Estudios en Diabetes, Unidad de Investigacion en Diabetes y Riesgo Cardiovascular, Centro de Investigacion en Salud Poblacional, Instituto Nacional de Salud Pública, Mexico City, Mexico.
¹⁹⁸ Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, CA, USA.
¹⁹⁹ Department of Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
²⁰⁰ Endocrine Division, Massachusetts General Hospital, Boston, MA, 2114, USA.
²⁰¹ The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
²⁰² Aging Research Center, Cinvestav Sede Sur, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, Mexico.
²⁰³ NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
²⁰⁴ Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
²⁰⁵ Unidad de Biología Molecular y Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
²⁰⁶ Corporal Michael J. Crescenz Philadelphia VA Medical Center, Philadelphia, PA, USA.
²⁰⁷ Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
²⁰⁸ Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
²⁰⁹ Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
²¹⁰ Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
²¹¹ Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 2114, USA.
²¹² Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, 2114, USA.
²¹³ Department of Epidemiology and Biostatistics, Imperial College London, St Mary's Campus, London, UK.
²¹⁴ Research Division, National Skin Centre, Singapore.
²¹⁵ Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

PMID: 40778152
PMCID: PMC12330429
DOI: 10.1101/2025.07.21.25331778

Abstract

Background: Polygenic risk scores (PRSs) improve type 2 diabetes (T2D) prediction beyond clinical risk factors but perform poorly in non-European populations, where T2D burden is often higher, undermining their global clinical utility.

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 97·5^th 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.

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Conflict of interest statement

H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reports research grants from Eli Lilly, Novo Nordisk, and Hanmi Pharmaceutical; grants to support continuing education programs from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Zuellig, and Jiangsu Hanson; and consulting fees from Abbott, Bayer, Biolinq, Eli Lilly, Novo Nordisk, Pfizer, Shionogi, and Zealand. M.S.U. has consulting activity and research funded in collaboration with Novo Nordisk. A.K.M. has research funded in collaboration with Novo Nordisk. M.S.U. has research funded in collaboration with Novo Nordisk and is an unpaid research collaborator with AstraZeneca. J.M.M. has research funded in collaboration with Novo Nordisk. S.R.P. has had research funded by Philips Respironics and consulting fees from Apnimed, Bayer, Philips Respironics, Mineralys, and SleepRes. M.A.N. ‘s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the National Institutes of Health to support open science research. He also currently owns stock in Character Bio and Neuron23 Inc.

Figures

**Fig.1 |. Overall analysis approach.**
a, Overview of the 125 T2D GWAS datasets, variant sets, and pairwise LD information used to generate five ancestry-specific T2D GWAS meta-analyses and 20 LD reference panels for PRSs training. b, Independent, ancestry-specific cohorts used to train the PRS models and select the optimal continuous shrinkage prior from five phi values (i.e., 0·01, 0·001, 1×10⁻⁴, 1×10⁻⁵, 1×10⁻⁶) based on predictive performance. Single-ancestry PRSs using GWAS summary statistics and LD panels matched to the validation ancestry or using data from the EAS or EUR ancestries. Multi-ancestry PRSs jointly modeled GWAS summary statistics and LD panels from all five ancestry groups. c, Set of 23 ancestry-specific and independent cohorts used to validate the 18 best-performing PRS. d, Evaluation of PRS predictive performance, including: i) incremental AUC, calculated as the difference between the AUC of the full model (PRS + covariates) and the model without the PRS, ii) proportion of variation in T2D status explained by the PRS, estimated using Nagelkerke’s r², iii) odds ratio per standard deviation (OR per SD) of the PRS distribution or odds ratio (OR) comparing PRS distribution extremes relative to the interquartile range.

**Fig. 2 |. Performance of the T2D PRSs in the validation cohorts across ancestry groups.**
a–e: Incremental AUC (iAUC) of the T2D PRS in the validation cohorts across ancestry groups: a, AFR, b, AMR, c, EAS, d, EUR, e, SAS. For each ancestry, the best-performing single-ancestry and multi-ancestry PRSs were evaluated. Each bar represents a single cohort. Bar colors represent the ancestry group: purple for AFR, yellow for AMR, green for EAS, red for EUR, and blue for SAS. Line colors represent the ancestry of the T2D GWAS summary statistics and LD panels used to train the PRS, using the same color codes for single-ancestry PRSs, and black for multi-ancestry PRSs *De Long test p<0·05. f–j: Odds ratio from the meta-analysis of validation cohorts across ancestry groups: f, AFR, g, AMR, h, EAS, i, EUR, j, SAS. Points represent the odds ratio per standard deviation (OR per SD) of the PRS distribution or the odds ratio (OR) comparing different PRS distribution extremes relative to the interquartile range. Error bars show the 95% confidence intervals (95% CI). Point colors represent the ancestry of the T2D GWAS summary statistics and LD panels used to train the PRS. *De Long p<0.05.

**Fig. 3 |. Performance of D-PRISM multi-ancestry PRSs compared to published T2D PRSs from the PGS Catalog and other sources in the All of Us cohort.**
a–e: Incremental AUC (iAUC) across ancestry groups: a, AFR, b, AMR, c, EAS, d, EUR, e, SAS. Black bars highlight this study’s multi-ancestry PRSs. *De Long p<0.05; **Bonferroni-corrected De Long p<9×10⁻⁴.

**Fig. 4 |. Association of D-PRISM multi-ancestry PRS with common complications of diabetes in the All of Us cohort.**
Odds ratio of this study’s multi-ancestry PRS for the following outcomes: CAD (cardiovascular disease), IS (ischemic stroke), DN (diabetic nephropathy), ESDN (end-stage diabetic nephropathy), DR (diabetic retinopathy), and PDR (proliferative diabetic retinopathy). Points represent the odds ratios per standard deviation (OR per SD) and are colored according to the genetic ancestry of the individuals tested: purple for AFR, yellow for AMR, and red for EUR. Error bars show the 95% confidence intervals (95% CI).

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References

1. Magliano Dianna J., Boyko Edward J., IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS. 2021.
1. Mercader JM, Ng MCY, Manning AK, Rich SS. Predicting diabetes risk in diverse populations: what next? Lancet Diabetes Endocrinol 2021; 9: 808–10. - PMC - PubMed
1. Suzuki K, Hatzikotoulas K, Southam L, et al. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature 2024; 627: 347–57. - PMC - PubMed
1. Udler MS, McCarthy MI, Florez JC, Mahajan A. Genetic Risk Scores for Diabetes Diagnosis and Precision Medicine. Endocr Rev 2019; 40: 1500–20. - PMC - PubMed
1. Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009; 374: 1677–86. - PMC - PubMed

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

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

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