{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T22:40:25Z","timestamp":1776379225060,"version":"3.51.2"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01HL089856, R01HL089897"],"award-info":[{"award-number":["R01HL089856, R01HL089897"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Population stratification is one of the major sources of confounding in genetic association studies, potentially causing false-positive and false-negative results. Here, we present a novel approach for the identification of population substructure in high-density genotyping data\/next generation sequencing data. The approach exploits the co-appearances of rare genetic variants in individuals. The method can be applied to all available genetic loci and is computationally fast. Using sequencing data from the 1000 Genomes Project, the features of the approach are illustrated and compared to existing methodology (i.e. EIGENSTRAT). We examine the effects of different cutoffs for the minor allele frequency on the performance of the approach. We find that our approach works particularly well for genetic loci with very small minor allele frequencies. The results suggest that the inclusion of rare-variant data\/sequencing data in our approach provides a much higher resolution picture of population substructure than it can be obtained with existing methodology. Furthermore, in simulation studies, we find scenarios where our method was able to control the type 1 error more precisely and showed higher power.<\/jats:p><jats:p>Availability and implementation:<\/jats:p><jats:p>Contact: \u00a0dmitry.prokopenko@uni-bonn.de<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv752","type":"journal-article","created":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T02:19:20Z","timestamp":1451614760000},"page":"1366-1372","source":"Crossref","is-referenced-by-count":67,"title":["Utilizing the Jaccard index to reveal population stratification in sequencing data: a simulation study and an application to the 1000 Genomes Project"],"prefix":"10.1093","volume":"32","author":[{"given":"Dmitry","family":"Prokopenko","sequence":"first","affiliation":[{"name":"1 Institute of Genomic Mathematics, University of Bonn, Bonn, Germany,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"Hecker","sequence":"additional","affiliation":[{"name":"1 Institute of Genomic Mathematics, University of Bonn, Bonn, Germany,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin K.","family":"Silverman","sequence":"additional","affiliation":[{"name":"2 Channing Division of Network Medicine, Brigham and Women\u2019s Hospital,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Pagano","sequence":"additional","affiliation":[{"name":"3 Department of Biostatistics, Harvard School of Public Health, Boston, USA,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus M.","family":"N\u00f6then","sequence":"additional","affiliation":[{"name":"4 Institute of Human Genetics, University of Bonn, Bonn, Germany,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Dina","sequence":"additional","affiliation":[{"name":"5 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) Unit\u00e9 Mixte de Recherche (UMR) 1087, l\u2019institut du thorax, Nantes, France,"},{"name":"6 Centre National de la Recherche Scientifique (CNRS) UMR 6291, l\u2019institut du thorax, Nantes, France,"},{"name":"7 Universit\u00e9 de Nantes, l\u2019institut du thorax, Nantes, France and"},{"name":"8 Centre Hospitalier Universitaire (CHU) de Nantes, l\u2019institut du thorax, Service de Cardiologie, Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Lange","sequence":"additional","affiliation":[{"name":"2 Channing Division of Network Medicine, Brigham and Women\u2019s Hospital,"},{"name":"3 Department of Biostatistics, Harvard School of Public Health, Boston, USA,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heide Loehlein","family":"Fier","sequence":"additional","affiliation":[{"name":"1 Institute of Genomic Mathematics, University of Bonn, Bonn, Germany,"},{"name":"3 Department of Biostatistics, Harvard School of Public Health, Boston, USA,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,12,31]]},"reference":[{"key":"2023020112214111200_btv752-B1","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1101\/gr.094052.109","article-title":"Fast model-based estimation of ancestry in unrelated individuals","volume":"19","author":"Alexander","year":"2009","journal-title":"Genome Res"},{"key":"2023020112214111200_btv752-B2","doi-asserted-by":"crossref","first-page":"e46519","DOI":"10.1371\/journal.pone.0046519","article-title":"Rare and low frequency variant stratification in the UK population: description and impact on association tests","volume":"7","author":"Babron","year":"2012","journal-title":"PLoS One"},{"key":"2023020112214111200_btv752-B3","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1186\/1753-6561-5-S9-S8","article-title":"Population structure analysis using rare and common functional variants","volume":"5","author":"Baye","year":"2011","journal-title":"BMC Proc"},{"key":"2023020112214111200_btv752-B4","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/ng1104-1129","article-title":"Genomic control to the extreme","volume":"36","author":"Devlin","year":"2004","journal-title":"Nat. Genet"},{"key":"2023020112214111200_btv752-B5","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/j.0006-341X.1999.00997.x","article-title":"Genomic control for association studies","volume":"55","author":"Devlin","year":"1999","journal-title":"Biometrics"},{"key":"2023020112214111200_btv752-B6","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1086\/516842","article-title":"A simple and improved correction for population stratification in case-control studies","volume":"80","author":"Epstein","year":"2007","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B7","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ajhg.2012.06.004","article-title":"A permutation procedure to correct for confounders in case-control studies, including tests of rare variation","volume":"91","author":"Epstein","year":"2012","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B8","doi-asserted-by":"crossref","first-page":"857","DOI":"10.2307\/2528823","article-title":"A general coefficient of similarity and some of its properties","volume":"27","author":"Gower","year":"1971","journal-title":"Biometrics"},{"key":"2023020112214111200_btv752-B9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF02289162","article-title":"Some necessary conditions for common factor analysis","volume":"19","author":"Guttman","year":"1954","journal-title":"Psychometrika"},{"key":"2023020112214111200_btv752-B10","doi-asserted-by":"crossref","first-page":"e1001289","DOI":"10.1371\/journal.pgen.1001289","article-title":"A new testing strategy to identify rare variants with either risk or protective effect on disease","volume":"7","author":"Ionita-Laza","year":"2011","journal-title":"PLoS Genet"},{"key":"2023020112214111200_btv752-B11","first-page":"223","article-title":"Nouvelles recherches sur la distribution florale","volume":"44","author":"Jaccard","year":"1908","journal-title":"Bull. Soc. Vaud. Des. Sci. Nat"},{"key":"2023020112214111200_btv752-B12","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1126\/science.1217283","article-title":"Recent explosive human population growth has resulted in an excess of rare genetic variants","volume":"336","author":"Keinan","year":"2012","journal-title":"Science"},{"key":"2023020112214111200_btv752-B13","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.1073\/pnas.0812824106","article-title":"Power of deep, all-exon resequencing for discovery of human trait genes","volume":"106","author":"Kryukov","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023020112214111200_btv752-B14","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/0013164490501004","article-title":"Assessing sampling variation relative to number-of-factors criteria","volume":"50","author":"Lambert","year":"1990","journal-title":"Educ. Psychol. Meas"},{"key":"2023020112214111200_btv752-B15","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/gepi.20434","article-title":"Discovering genetic ancestry using spectral graph theory","volume":"34","author":"Lee","year":"2010","journal-title":"Genet. Epidemiol"},{"key":"2023020112214111200_btv752-B16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/gepi.21621","article-title":"Sparse principal component analysis for identifying ancestry-informative markers in genome-wide association studies","volume":"36","author":"Lee","year":"2012","journal-title":"Genet. Epidemiol"},{"key":"2023020112214111200_btv752-B17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ajhg.2008.06.024","article-title":"Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data","volume":"83","author":"Li","year":"2008","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/gepi.20296","article-title":"Improved correction for population stratification in genomewide association studies by identifying hidden population structures","volume":"32","author":"Li","year":"2008","journal-title":"Genet. Epidemiol"},{"key":"2023020112214111200_btv752-B19","doi-asserted-by":"crossref","first-page":"e1000384","DOI":"10.1371\/journal.pgen.1000384","article-title":"A groupwise association test for rare mutations using a weighted sum statistic","volume":"5","author":"Madsen","year":"2009","journal-title":"PLoS Genet"},{"key":"2023020112214111200_btv752-B20","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/ng.1074","article-title":"Differential confounding of rare and common variants in spatially structured populations","volume":"44","author":"Mathieson","year":"2012","journal-title":"Nat. Genet"},{"key":"2023020112214111200_btv752-B21","doi-asserted-by":"crossref","first-page":"e190","DOI":"10.1371\/journal.pgen.0020190","article-title":"Population structure and eigenanalysis","volume":"2","author":"Patterson","year":"2006","journal-title":"PLoS Genet"},{"key":"2023020112214111200_btv752-B22","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.ajhg.2010.04.005","article-title":"Pooled Association Tests for Rare Variants in Exon-Resequencing Studies","volume":"86","author":"Price","year":"2010","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B23","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/ng1847","article-title":"Principal components analysis corrects for stratification in genome-wide association studies","volume":"38","author":"Price","year":"2006","journal-title":"Nat. Genet"},{"key":"2023020112214111200_btv752-B24","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ajhg.2008.06.005","article-title":"Long-range LD can confound genome scans in admixed populations","volume":"83","author":"Price","year":"2008","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B25","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/nrg2813","article-title":"New approaches to population stratification in genome-wide association studies","volume":"11","author":"Price","year":"2010","journal-title":"Nat. Rev. Genet"},{"key":"2023020112214111200_btv752-B26","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1086\/321272","article-title":"Are rare variants responsible for susceptibility to complex diseases?","volume":"69","author":"Pritchard","year":"2001","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B27","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1093\/hmg\/11.20.2417","article-title":"The allelic architecture of human disease genes: common disease-common variant\u2026 or not?","volume":"11","author":"Pritchard","year":"2002","journal-title":"Hum. Mol. Genet"},{"key":"2023020112214111200_btv752-B28","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1086\/302959","article-title":"Association mapping in structured populations","volume":"67","author":"Pritchard","year":"2000","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/1098-2272(200101)20:1<4::AID-GEPI2>3.0.CO;2-T","article-title":"Detecting association in a case-control study while correcting for population stratification","volume":"20","author":"Reich","year":"2001","journal-title":"Genet. Epidemiol"},{"key":"2023020112214111200_btv752-B30","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1086\/318195","article-title":"Accounting for unmeasured population substructure in case-control studies of genetic association using a novel latent-class model","volume":"68","author":"Satten","year":"2001","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B31","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1162\/089976698300017467","article-title":"Nonlinear component analysis as a kernel eigenvalue problem","volume":"10","author":"Sch\u00f6lkopf","year":"1998","journal-title":"Neural Comput"},{"key":"2023020112214111200_btv752-B32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An integrated map of genetic variation from 1,092 human genomes","volume":"491","author":"The 1000 Genomes Project Consortium","year":"2012","journal-title":"Nature"},{"key":"2023020112214111200_btv752-B33","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"The 1000 Genomes Project Consortium","year":"2015","journal-title":"Nature"},{"key":"2023020112214111200_btv752-B34","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/nature14962","article-title":"The UK10K project identifies rare variants in health and disease","volume":"526","author":"The UK10K Consortium","year":"2015","journal-title":"Nature"},{"key":"2023020112214111200_btv752-B35","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ajhg.2011.05.029","article-title":"Rare-variant association testing for sequencing data with the sequence kernel association test","volume":"89","author":"Wu","year":"2011","journal-title":"Am. J. Hum. Genet"},{"key":"2023020112214111200_btv752-B36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/gepi.21691","article-title":"Adjustment for population stratification via principal components in association analysis of rare variants","volume":"37","author":"Zhang","year":"2013","journal-title":"Genet. Epidemiol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/9\/1366\/49019125\/bioinformatics_32_9_1366.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/9\/1366\/49019125\/bioinformatics_32_9_1366.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T14:56:41Z","timestamp":1718290601000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/9\/1366\/1743877"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,31]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv752","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,5,1]]},"published":{"date-parts":[[2015,12,31]]}}}