{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:30:32Z","timestamp":1778830232501,"version":"3.51.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Sciences and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18km0605001"],"award-info":[{"award-number":["JP18km0605001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19km0405215"],"award-info":[{"award-number":["JP19km0405215"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins. Variance component analysis of Rsq revealed that the increased imputed-genotype certainty (dosages closer to 0, 1 or 2) caused upward bias, indicating some systemic bias in the imputation. Through systematic simulations using different template switching rates (\u03b8\u00a0value) in the hidden Markov model, we revealed that the lower \u03b8 value increased the imputed-genotype certainty and Rsq; however, dosage r2 was insensitive to the \u03b8 value, thereby causing a deviation. In simulated reference panels with different sizes and ancestral diversities, the \u03b8 value estimates from Minimac decreased with the size of a single ancestry and increased with the ancestral diversity. Thus, Rsq could be deviated from dosage r2 for a subpopulation in the multi-ancestry panel, and the deviation represents different imputed-dosage distributions. Finally, despite the impact of the \u03b8 value, distant ancestries in the reference panel contributed only a few additional variants passing a predefined Rsq threshold. We conclude that the \u03b8 value substantially impacts the imputed dosage and the imputation quality metric value.<\/jats:p>","DOI":"10.1093\/bib\/bbad509","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:26:43Z","timestamp":1704932803000},"source":"Crossref","is-referenced-by-count":9,"title":["Genotype imputation accuracy and the quality metrics of the minor ancestry in multi-ancestry reference panels"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-8551","authenticated-orcid":false,"given":"Mingyang","family":"Shi","sequence":"first","affiliation":[{"name":"Laboratory of Complex Trait Genomics , Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, , Tokyo, Japan"},{"name":"The University of Tokyo , Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, , Tokyo, 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