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PWAS relies on an ancestry-matched reference panel to model the impact of genetically determined protein expression on phenotype. However, reference panels from underrepresented populations remain relatively limited. We developed a multi-ancestry framework to enhance protein prediction in these populations by integrating diverse information-sharing strategies into a Multi-Ancestry Best-performing Model (MABM). Results indicated that MABM increased the prediction performance with higher performance observed in both cross-validation and an external dataset. Leveraging the Biobank Japan, we identified three times as many significant PWAS associations using MABM as using Lasso model. Notably, 47.5% of the MABM specific associations were reproduced in independent East Asian datasets with concordant effect sizes. Furthermore, MABM enhanced decision-making in gene\/protein prioritization for functional validation for complex traits by validating well-established associations and uncovering novel trait-related candidates. The benefits of MABM were further validated in additional ancestries and demonstrated in brain tissue-based PWAS, underscoring its broad applicability. Our findings close critical gaps in multi-omics research among underrepresented populations and facilitate trait-relevant protein discovery in underrepresented populations.<\/jats:p>","DOI":"10.1093\/bib\/bbaf707","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T12:54:09Z","timestamp":1766235249000},"source":"Crossref","is-referenced-by-count":0,"title":["Cross-ancestry information transfer framework improves protein abundance prediction and protein-trait association identification"],"prefix":"10.1093","volume":"27","author":[{"given":"Wenli","family":"Zhai","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine , 866 Yuhangtang Road, Hangzhou , Zhejiang 310058,","place":["China"]},{"name":"Zhejiang Key Laboratory of Intelligent Preventive Medicine , 866 Yuhangtang Road, Hangzhou, Zhejiang 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310058,","place":["China"]},{"name":"Zhejiang Key Laboratory of Intelligent Preventive Medicine , 866 Yuhangtang Road, Hangzhou, Zhejiang 310058,","place":["China"]}]},{"given":"Yuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital and School of Public Health, Zhejiang University School of Medicine , 866 Yuhangtang Road, Hangzhou , Zhejiang 310058,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3562-8861","authenticated-orcid":false,"given":"Jiadong","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute for Financial Studies, Shandong University , 27 Shanda Nanlu, Jinan, Shandong 250100 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9938-3627","authenticated-orcid":false,"given":"Lang","family":"Wu","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawai'i Cancer Center, University of Hawai'i at M\u0101noa , 701 Ilalo Street, Honolulu, HI 96813 ,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-7945","authenticated-orcid":false,"given":"An","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , 13 Hangkong Road, Wuhan, Hubei 430030 ,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-8734","authenticated-orcid":false,"given":"Eric R","family":"Gamazon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center , 2525 West End Avenue, Suite 700, Nashville, TN 37203 ,","place":["United States"]},{"name":"Clare Hall, University of Cambridge , Herschel Road, Cambridge CB3 9AL ,","place":["United 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