{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:24Z","timestamp":1772138064042,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T00:00:00Z","timestamp":1706054400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israeli Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Polygenic risk scores (PRSs) predict individuals\u2019 genetic risk of developing complex diseases. They summarize the effect of many variants discovered in genome-wide association studies (GWASs). However, to date, large GWASs exist primarily for the European population and the quality of PRS prediction declines when applied to other ethnicities. Genetic profiling of individuals in the discovery set (on which the GWAS was performed) and target set (on which the PRS is applied) is typically done by SNP arrays that genotype a fraction of common SNPs. Therefore, a key step in GWAS analysis and PRS calculation is imputing untyped SNPs using a panel of fully sequenced individuals. The imputation results depend on the ethnic composition of the imputation panel. Imputing genotypes with a panel of individuals of the same ethnicity as the genotyped individuals typically improves imputation accuracy. However, there has been no systematic investigation into the influence of the ethnic composition of imputation panels on the accuracy of PRS predictions when applied to ethnic groups that differ from the population used in the GWAS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We estimated the effect of imputation of the target set on prediction accuracy of PRS when the discovery and the target sets come from different ethnic groups. We analyzed binary phenotypes on ethnically distinct sets from the UK Biobank and other resources. We generated ethnically homogenous panels, imputed the target sets, and generated PRSs. Then, we assessed the prediction accuracy obtained from each imputation panel. Our analysis indicates that using an imputation panel matched to the ethnicity of the target population yields only a marginal improvement and only under specific conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The source code used for executing the analyses is this paper is available at https:\/\/github.com\/Shamir-Lab\/PRS-imputation-panels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae036","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T15:25:15Z","timestamp":1705764315000},"source":"Crossref","is-referenced-by-count":1,"title":["The predictive capacity of polygenic risk scores for disease risk is only moderately influenced by imputation panels tailored to the target population"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-4766","authenticated-orcid":false,"given":"Hagai","family":"Levi","sequence":"first","affiliation":[{"name":"The Blavatnik School of Computer Science, Tel Aviv University , Tel Aviv 69978, Israel"},{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University , Tel Aviv 69978, Israel"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-1286","authenticated-orcid":false,"given":"Ran","family":"Elkon","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University , Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University , Tel Aviv 69978, Israel"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-9870","authenticated-orcid":false,"given":"Ron","family":"Shamir","sequence":"additional","affiliation":[{"name":"The Blavatnik School of Computer Science, Tel Aviv University , Tel Aviv 69978, Israel"}]}],"member":"286","published-online":{"date-parts":[[2024,1,23]]},"reference":[{"key":"2024020805384058900_btae036-B1","doi-asserted-by":"crossref","first-page":"6733","DOI":"10.1038\/s41598-017-06905-6","article-title":"Inclusion of population-specific reference panel from India to the 1000 genomes phase 3 panel improves imputation accuracy","volume":"7","author":"Ahmad","year":"2017","journal-title":"Sci Rep"},{"key":"2024020805384058900_btae036-B2","first-page":"1","article-title":"Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases","volume":"10","author":"An","year":"2019","journal-title":"Nat Commun"},{"key":"2024020805384058900_btae036-B3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"2024020805384058900_btae036-B4","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41576-018-0065-3","article-title":"UK Biobank\u2013a new era in genomic medicine","volume":"19","author":"Bahcall","year":"2018","journal-title":"Nat Rev Genet"},{"key":"2024020805384058900_btae036-B5","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1093\/bib\/bbz108","article-title":"Genotype imputation and reference panel: a systematic evaluation on haplotype size and diversity","volume":"21","author":"Bai","year":"2020","journal-title":"Brief Bioinform"},{"key":"2024020805384058900_btae036-B6","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1101\/gr.154831.113","article-title":"Estimating and interpreting FST: the impact of rare variants","volume":"23","author":"Bhatia","year":"2013","journal-title":"Genome Res"},{"key":"2024020805384058900_btae036-B7","author":"Cahoon","year":"2023"},{"key":"2024020805384058900_btae036-B8","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1038\/ncomms5835","article-title":"Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins","volume":"5","author":"Carmi","year":"2014","journal-title":"Nat Commun"},{"key":"2024020805384058900_btae036-B9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13073-020-00801-x","article-title":"Genotype imputation and variability in polygenic risk score estimation","volume":"12","author":"Chen","year":"2020","journal-title":"Genome Med"},{"key":"2024020805384058900_btae036-B10","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"2024020805384058900_btae036-B11","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nmeth.1785","article-title":"A linear complexity phasing method for thousands of genomes","volume":"9","author":"Delaneau","year":"2011","journal-title":"Nat Methods"},{"key":"2024020805384058900_btae036-B12","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1038\/s41588-018-0205-x","article-title":"Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits","volume":"50","author":"Evangelou","year":"2018","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B13","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/j.ajhg.2022.07.012","article-title":"Extent to which array genotyping and imputation with large reference panels approximate deep whole-genome sequencing","volume":"109","author":"Hanks","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2024020805384058900_btae036-B14","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41593-018-0326-7","article-title":"Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions","volume":"22","author":"Howard","year":"2019","journal-title":"Nat Neurosci"},{"key":"2024020805384058900_btae036-B15","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1534\/g3.111.001198","article-title":"Genotype imputation with thousands of genomes","volume":"1","author":"Howie","year":"2011","journal-title":"G3 (Bethesda)"},{"key":"2024020805384058900_btae036-B16","doi-asserted-by":"crossref","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet"},{"key":"2024020805384058900_btae036-B17","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1038\/s41588-019-0512-x","article-title":"Comparative genetic architectures of schizophrenia in East Asian and European populations","volume":"51","author":"Lam","year":"2019","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B18","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1038\/ncomms3739","article-title":"Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder","volume":"4","author":"Lencz","year":"2013","journal-title":"Nat Commun"},{"key":"2024020805384058900_btae036-B19","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s00439-018-1886-z","article-title":"High-depth whole genome sequencing of an Ashkenazi Jewish reference panel: enhancing sensitivity, accuracy, and imputation","volume":"137","author":"Lencz","year":"2018","journal-title":"Hum Genet"},{"key":"2024020805384058900_btae036-B20","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/jmg-2023-109185","article-title":"Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel","volume":"60","author":"Levi","year":"2023","journal-title":"J Med Genet"},{"key":"2024020805384058900_btae036-B21","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/s41588-018-0241-6","article-title":"Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps","volume":"50","author":"Mahajan","year":"2018","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B22","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41588-019-0379-x","article-title":"Clinical use of current polygenic risk scores may exacerbate health disparities","volume":"51","author":"Martin","year":"2019","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B23","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ng.3643","article-title":"A reference panel of 64,976 haplotypes for genotype imputation","volume":"48","author":"McCarthy","year":"2016","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B24","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1534\/g3.113.007161","article-title":"Imputation-based genomic coverage assessments of current human genotyping arrays","volume":"3","author":"Nelson","year":"2013","journal-title":"G3 (Bethesda)"},{"key":"2024020805384058900_btae036-B34","first-page":"1755","volume-title":"Sci Rep","author":"Nguyen","year":"2022"},{"key":"2024020805384058900_btae036-B25","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1038\/ng.201","article-title":"Identification of loci associated with schizophrenia by genome-wide association and follow-up","volume":"40","author":"O\u2019Donovan","year":"2008","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B26","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nature13595","article-title":"Biological insights from 108 schizophrenia-associated genetic loci","volume":"511","author":"Ripke","year":"2014","journal-title":"Nature"},{"key":"2024020805384058900_btae036-B27","first-page":"186","article-title":"Community engagement and informed consent in the International HapMap project","volume":"10","author":"Rotimi","year":"2007","journal-title":"Community Genet"},{"key":"2024020805384058900_btae036-B28","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41588-021-00931-x","article-title":"A cross-population atlas of genetic associations for 220 human phenotypes","volume":"53","author":"Sakaue","year":"2021","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B29","doi-asserted-by":"crossref","first-page":"100332","DOI":"10.1016\/j.xgen.2023.100332","article-title":"Performance and accuracy evaluation of reference panels for genotype imputation in Sub-Saharan African populations","volume":"3","author":"Sengupta","year":"2023","journal-title":"Cell Genomics"},{"key":"2024020805384058900_btae036-B30","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nature08192","article-title":"Common variants on chromosome 6p22.1 are associated with schizophrenia","volume":"460","author":"Shi","year":"2009","journal-title":"Nature"},{"key":"2024020805384058900_btae036-B31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1159\/000489758","article-title":"Comprehensive assessment of genotype imputation performance","volume":"83","author":"Shi","year":"2018","journal-title":"Hum Hered"},{"key":"2024020805384058900_btae036-B32","doi-asserted-by":"crossref","first-page":"724037","DOI":"10.3389\/fgene.2021.724037","article-title":"Assessment of imputation quality: comparison of phasing and imputation algorithms in real data","volume":"12","author":"Stahl","year":"2021","journal-title":"Front Genet"},{"key":"2024020805384058900_btae036-B33","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","article-title":"Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program","volume":"590","author":"Taliun","year":"2021","journal-title":"Nature"},{"key":"2024020805384058900_btae036-B35","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels","volume":"45","author":"Willer","year":"2013","journal-title":"Nat Genet"},{"key":"2024020805384058900_btae036-B36","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev.genom.9.081307.164242","article-title":"Genotype imputation","volume":"10","author":"Yun","year":"2009","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2024020805384058900_btae036-B37","first-page":"352","article-title":"Practical consideration of genotype imputation: sample size, window size, reference choice, and untyped rate","volume":"4","author":"Zhang","year":"2011","journal-title":"Stat Interface"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae036\/56370381\/btae036.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/2\/btae036\/56619439\/btae036.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/2\/btae036\/56619439\/btae036.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T01:03:54Z","timestamp":1707354234000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae036\/7587512"}},"subtitle":[],"editor":[{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2024,1,23]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae036","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.08.29.23294769","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,2,1]]},"published":{"date-parts":[[2024,1,23]]},"article-number":"btae036"}}