{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:04:27Z","timestamp":1784307867721,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,15]]},"group-title":"Genetic and Genomic Medicine","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israeli Science Foundation","doi-asserted-by":"crossref","award":["3165\/19"],"award-info":[{"award-number":["3165\/19"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tel Aviv University Center for AI and Data Science"},{"name":"Cancer Biology Research Center, Djerassi Oncology Center"},{"name":"Edmond J. Safra Center for Bioinformatics"},{"name":"Koret-UC Berkeley-Tel Aviv University Initiative"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Polygenic risk scores (PRSs), which quantify inherited susceptibility to complex traits and diseases, have emerged as valuable tools for risk stratification and precision medicine. Despite their promise, PRS developed on European cohorts often demonstrate substantially reduced predictive accuracy in non-European populations, due to differences in genetic architecture. The disproportionate representation of European ancestry cohorts in genome-wide association studies (GWAS) leads to inequitable deployment of PRS technologies across diverse populations. Here, we introduce PRANA (Polygenic Risk Adaptation via Neural-network Architecture), a deep learning framework that adapts an existing PRS developed on one population to other ancestries. Unlike methods that require large-scale GWAS in the target population, PRANA leverages pre-trained PRS models derived from European cohorts and adapts them using modestly sized cohorts from the target population.<\/jats:p>\n                <jats:p>We evaluated PRANA on seven complex traits in South Asian, East Asian and Ashkenazi Jewish populations, as well as in selected smaller East Asian subpopulations where the scarcity of training data poses a particular challenge. PRANA mostly improved predictive performance of the baseline PRS models by 5%-20% in terms of effect size (\u03b2) and Nagelkerke\u2019s R\u00b2, and, in most cases, outperformed existing cross-ancestry multi-PRS approaches. These results highlight PRANA as a scalable and practical strategy to reduce disparities in genomic risk prediction and advance the equitable application of PRS in diverse populations.<\/jats:p>","DOI":"10.64898\/2026.07.12.26357860","type":"posted-content","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T17:25:27Z","timestamp":1784136327000},"source":"Crossref","is-referenced-by-count":0,"title":["PRANA: A Deep Learning Method for Adapting Polygenic Risk Scores to Diverse Ethnic Groups"],"prefix":"10.64898","author":[{"given":"Hagai","family":"Levi","sequence":"first","affiliation":[{"name":"Blavatnik School of Computer Science and AI, Tel Aviv University, Tel Aviv, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK, CB1 8RN, 2 Worts\u2019 Causeway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjeet K.","family":"Bolla","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK, CB1 8RN, 2 Worts\u2019 Causeway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Dennis","sequence":"additional","affiliation":[{"name":"Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK, CB1 8RN, 2 Worts\u2019 Causeway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene L.","family":"Andrulis","sequence":"additional","affiliation":[{"name":"Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5, 600 University Avenue"},{"name":"Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada, M5S 1A8, 1 King\u2019s College Circle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Antonenkova","sequence":"additional","affiliation":[{"name":"N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus, 223040, Settlement of Lesnoy-2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Hang","family":"Au","sequence":"additional","affiliation":[{"name":"Molecular Pathology Division, Department of Pathology, Hong Kong Sanatorium and Hospital, Hong Kong, 2 Village Rd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelie","family":"Augustinsson","sequence":"additional","affiliation":[{"name":"Oncology, Department of Clinical Sciences in Lund, Lund University, Lund, Sweden, 221 85, Barngatan 4, Sk\u00e5nes universitetssjukhus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E. Beane","family":"Freeman","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA, 20850, 9609 Medical Center Dr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Behrens","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 69120, Im Neuenheimer Feld 280"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Bermisheva","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics\u2014Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia, 450054, 71 prosp. Oktyabrya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Bodelon","sequence":"additional","affiliation":[{"name":"Department of Population Science, American Cancer Society, Atlanta, GA, USA, 30303, 250 Williams Street NW"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia V.","family":"Bogdanova","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Hannover Medical School, Hannover, Germany, 30625, Carl-Neuberg-Stra\u00dfe 1"},{"name":"Gynaecology Research Unit, Hannover Medical School, Hannover, Germany, 30625, Carl-Neuberg-Stra\u00dfe 1"},{"name":"N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus, 223040, Settlement of Lesnoy-2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stig E.","family":"Bojesen","sequence":"additional","affiliation":[{"name":"Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark, 2730, Herlev Ringvej 75"},{"name":"Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark, 2730, Herlev Ringvej 75"},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, 2200, Blegdamsvej 3B"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Brenner","sequence":"additional","affiliation":[{"name":"Cancer Prevention Graduate School, German Cancer Research Center (DKFZ), Heidelberg, Germany, 69120, Im Neuenheimer Feld 280"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian W.","family":"Brock","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, School of Medicine and Population Health, University of Shefield, Shefield, UK, S10 2TN, Western Bank"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[{"name":"Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany, 44789, B\u00fcrkle-de-la-Camp-Platz 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Byers","sequence":"additional","affiliation":[{"name":"North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary\u2019s Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK, M13 9WL, Oxford Road"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola J.","family":"Camp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA, 84112, 2000 Circle of Hope"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Castelao","sequence":"additional","affiliation":[{"name":"Oncology and Genetics Unit, Instituto de Investigaci\u00f3n Sanitaria Galicia Sur (IIS-GS), SERGAS, Vigo, Spain, 36312, Estrada Clara Campoamor n\u00b0 341"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yeob","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea, 03080, 103 Daehak-ro, Jongno-gu Seoul"},{"name":"Cancer Research Institute, Seoul National University, Seoul, Korea, 03080, 103 Daehak-ro, Jongno-gu Seoul"},{"name":"Institute of Health Policy and Management, Seoul National University Medical Research Center, Seoul, Korea, 03080, 103 Daehak-ro, Jongno-gu Seoul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NBCS Collaborators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah V.","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA, 84112, 2000 Circle of Hope"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergus J.","family":"Couch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA, 55905, 200 First St. SW"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Czene","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, 171 65, Karolinska Univ Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Daly","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA, 19111, 333 Cottman Ave"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Devilee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands, 2333 ZA, Albinusdreef 2"},{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands, 2333 ZA, Albinusdreef 2, P.O. Box 9600, 2300 RC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"D\u00f6rk","sequence":"additional","affiliation":[{"name":"Gynaecology Research Unit, Hannover Medical School, Hannover, Germany, 30625, Carl-Neuberg-Stra\u00dfe 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Heather","family":"Eliassen","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA, 02115, 181 Longwood Avenue, 3rd Floor"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA, 02115, 677 Huntington Avenue"},{"name":"Department of Nutrition, Harvard T.H. 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Box 2040, 3000 CA"},{"name":"Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands, 3015 CN, Wytemaweg 80, P.O. Box 2040, 3000 CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Hoppe","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany, 70376, Auerbachstr. 112"},{"name":"University of T\u00fcbingen, T\u00fcbingen, Germany, 72074, Geschwister-Scholl-Platz"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha J.","family":"Howell","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, University of Manchester, Manchester, UK, M13 9PL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ABCTB Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"SGBCC Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemi","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan, 464-8681, 1-1 Kanokoden, Chikusa-ku"},{"name":"Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 466-8550, 65 Tsurumai-cho, Showa-ku"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoki","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan, 104-0045, 5-1-1 Tsukiji, Chuo-ku"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jakubowska","sequence":"additional","affiliation":[{"name":"Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland, 71-252, Unii Lubelskiej 1"},{"name":"Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland, 71-252"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Jernstr\u00f6m","sequence":"additional","affiliation":[{"name":"Oncology, Department of Clinical Sciences in Lund, Lund University, Lund, Sweden, 221 85, Barngatan 4, Sk\u00e5nes universitetssjukhus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijai","family":"Joseph","sequence":"additional","affiliation":[{"name":"Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 10065, 1275 York Avenue"},{"name":"Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA, 10065, 1275 York Avenue"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Kaaks","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 69120, Im Neuenheimer Feld 280"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daehee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea, 03080, 103 Daehak-ro, Jongno-gu Seoul"},{"name":"Cancer Research Institute, Seoul National University, Seoul, Korea, 03080, 103 Daehak-ro, Jongno-gu Seoul"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elza K.","family":"Khusnutdinova","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Genetics\u2014Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, Ufa, Russia, 450054, 71 prosp. 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