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However, how to leverage such shared information more efficiently in association analysis is less investigated for traits in underrepresented populations. We here propose a statistical framework, trans-ethnic genetic risk score informed gene-based association mixed model (GAMM), by hierarchically modeling single-nucleotide polymorphism effects in the target population as a function of effects of the same trait in well-studied populations. GAMM powerfully integrates genetic similarity across distinct ancestral groups to enhance power in understudied populations, as confirmed by extensive simulations. We illustrate the usefulness of GAMM via the application to 13 blood cell traits (i.e. basophil count, eosinophil count, hematocrit, hemoglobin concentration, lymphocyte count, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular volume, monocyte count, neutrophil count, platelet count, red blood cell count and total white blood cell count) in Africans of the UK Biobank (n\u2009=\u20093204) while utilizing genetic overlap shared in Europeans (n\u2009=\u2009746\u00a0667) and East Asians (n\u2009=\u2009162\u00a0255). We discovered multiple new associated genes, which had otherwise been missed by existing methods, and revealed that the trans-ethnic information indirectly contributed much to the phenotypic variance. Overall, GAMM represents a flexible and powerful statistical framework of association analysis for complex traits in underrepresented populations by integrating trans-ethnic genetic similarity across well-studied populations, and helps attenuate health inequities in current genetics research for people of minority populations.<\/jats:p>","DOI":"10.1093\/bib\/bbad232","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T02:22:55Z","timestamp":1687141375000},"source":"Crossref","is-referenced-by-count":6,"title":["Leveraging trans-ethnic genetic risk scores to improve association power for complex traits in underrepresented populations"],"prefix":"10.1093","volume":"24","author":[{"given":"Haojie","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Biostatistics , School of Public Health, , Xuzhou, Jiangsu 221004 , China"},{"name":"Xuzhou Medical University , School of Public Health, , Xuzhou, Jiangsu 221004 , China"}]},{"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics , School of Public Health, , Xuzhou, Jiangsu 221004 , China"},{"name":"Xuzhou Medical University , School of Public Health, , Xuzhou, Jiangsu 221004 , China"}]},{"given":"Zhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics , School of Public Health, , Xuzhou, Jiangsu 221004 , China"},{"name":"Xuzhou Medical University , School of Public Health, , Xuzhou, Jiangsu 221004 , China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-3440","authenticated-orcid":false,"given":"Ping","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics , School of Public Health, , Xuzhou, Jiangsu 221004 , China"},{"name":"Xuzhou Medical University , School of Public Health, , Xuzhou, Jiangsu 221004 , China"},{"name":"Center for Medical Statistics and Data Analysis, Xuzhou Medical University , Xuzhou, Jiangsu, 221004 , China"},{"name":"Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University , Xuzhou, Jiangsu, 221004 , China"},{"name":"Key Laboratory of Environment and Health, Xuzhou Medical University , Xuzhou, Jiangsu, 221004 , China"},{"name":"Engineering Research Innovation Center of Biological Data Mining and Healthcare Transformation, Xuzhou Medical University , Xuzhou, Jiangsu, 221004 , China"}]}],"member":"286","published-online":{"date-parts":[[2023,6,17]]},"reference":[{"key":"2023072020165425800_ref1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41576-019-0127-1","article-title":"Benefits and limitations of genome-wide association studies","volume":"20","author":"Tam","year":"2019","journal-title":"Nat Rev Genet"},{"key":"2023072020165425800_ref2","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1038\/nn.4411","article-title":"Translating genome-wide association findings into new therapeutics for 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