{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:29:08Z","timestamp":1759962548573,"version":"3.41.2"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH129337"],"award-info":[{"award-number":["R01MH129337"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["P01HL120839","U01HL089897","U01HL089856","P01 HL132825"],"award-info":[{"award-number":["P01HL120839","U01HL089897","U01HL089856","P01 HL132825"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["2U01HG008685","R01HG008976"],"award-info":[{"award-number":["2U01HG008685","R01HG008976"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Genetic similarity matrices are commonly used to assess population substructure (PS) in genetic studies. Through simulation studies and by the application to whole-genome sequencing (WGS) data, we evaluate the performance of three genetic similarity matrices: the unweighted and weighted Jaccard similarity matrices and the genetic relationship matrix. We describe different scenarios that can create numerical pitfalls and lead to incorrect conclusions in some instances. We consider scenarios in which PS is assessed based on loci that are located across the genome (\u2018globally\u2019) and based on loci from a specific genomic region (\u2018locally\u2019). We also compare scenarios in which PS is evaluated based on loci from different minor allele frequency bins: common (&amp;gt;5%), low-frequency (5\u20130.5%) and rare (&amp;lt;0.5%) single-nucleotide variations (SNVs). Overall, we observe that all approaches provide the best clustering performance when computed based on rare SNVs. The performance of the similarity matrices is very similar for common and low-frequency variants, but for rare variants, the unweighted Jaccard matrix provides preferable clustering features. Based on visual inspection and in terms of standard clustering metrics, its clusters are the densest and the best separated in the principal component analysis of variants with rare SNVs compared with the other methods and different allele frequency cutoffs. In an application, we assessed the role of rare variants on local and global PS, using WGS data from multiethnic Alzheimer\u2019s disease data sets and European or East Asian populations from the 1000 Genome Project.<\/jats:p>","DOI":"10.1093\/bib\/bbac611","type":"journal-article","created":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T06:12:19Z","timestamp":1672467139000},"source":"Crossref","is-referenced-by-count":7,"title":["A comparison between similarity matrices for principal component analysis to assess population stratification in sequenced genetic data sets"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-9555","authenticated-orcid":false,"given":"Sanghun","family":"Lee","sequence":"first","affiliation":[{"name":"Harvard University Department of Biostatistics, T.H. Chan School of Public Health, , Boston, MA , USA"},{"name":"Brigham and Women\u2019s Hospital Channing Division of Network Medicine, , Boston, MA , USA"},{"name":"Dankook University Department of Medical Consilience, Division of Medicine, Graduate school, , Sout h Korea"},{"name":"NH Institute for Natural Product Research, Myungji Hospital , Sout h Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6008-2720","authenticated-orcid":false,"given":"Georg","family":"Hahn","sequence":"additional","affiliation":[{"name":"Harvard University Department of Biostatistics, T.H. Chan School of Public Health, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7918-089X","authenticated-orcid":false,"given":"Julian","family":"Hecker","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Channing Division of Network Medicine, , Boston, MA , USA"},{"name":"Harvard Medical School , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1515-9431","authenticated-orcid":false,"given":"Sharon M","family":"Lutz","sequence":"additional","affiliation":[{"name":"Harvard University Department of Biostatistics, T.H. Chan School of Public Health, , Boston, MA , USA"},{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Harvard Pilgrim Health Care Institute Department of Population Medicine, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Mullin","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Genetics and Aging Unit and McCance Center for Brain Health, Department of Neurology, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8621-3271","authenticated-orcid":false,"given":"Winston","family":"Hide","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Beth Israel Deaconess Medical Center Department of Pathology, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0108-124X","authenticated-orcid":false,"given":"Lars","family":"Bertram","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck L\u00fcbeck Interdisciplinary Platform for Genome Analytics, , L\u00fcbeck , Germany"},{"name":"University of Oslo Department of Psychology, , Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-0636","authenticated-orcid":false,"given":"Dawn L","family":"DeMeo","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital Channing Division of Network Medicine, , Boston, MA , USA"},{"name":"Harvard Medical School , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7032-1454","authenticated-orcid":false,"given":"Rudolph E","family":"Tanzi","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Massachusetts General Hospital Genetics and Aging Unit and McCance Center for Brain Health, Department of Neurology, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2620-1030","authenticated-orcid":false,"given":"Christoph","family":"Lange","sequence":"additional","affiliation":[{"name":"Harvard University Department of Biostatistics, T.H. Chan School of Public Health, , Boston, MA , USA"},{"name":"Brigham and Women\u2019s Hospital Channing Division of Network Medicine, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-5652","authenticated-orcid":false,"given":"Dmitry","family":"Prokopenko","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA , USA"},{"name":"Massachusetts General Hospital Genetics and Aging Unit and McCance Center for Brain Health, Department of Neurology, , Boston, MA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"2023011917123503000_ref1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/ng1607","article-title":"Demonstrating stratification in a European American population","volume":"37","author":"Campbell","year":"2005","journal-title":"Nat 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