{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:29:20Z","timestamp":1790504960033,"version":"4.1.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR056292"],"award-info":[{"award-number":["R01AR056292"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR057212"],"award-info":[{"award-number":["R01AR057212"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR065951"],"award-info":[{"award-number":["R01AR065951"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AR057212"],"award-info":[{"award-number":["P30AR057212"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AR007411-31A1"],"award-info":[{"award-number":["T32 AR007411-31A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autoimmune vitiligo is a complex disease involving polygenic risk from at least 50 loci previously identified by genome-wide association studies. The objectives of this study were to estimate and compare vitiligo heritability in European-derived patients using both family-based and \u2018deep imputation\u2019 genotype-based approaches. We estimated family-based heritability (h2FAM) by vitiligo recurrence among a total 8034 first-degree relatives (3776 siblings, 4258 parents or offspring) of 2122 unrelated vitiligo probands. We estimated genotype-based heritability (h2SNP) by deep imputation to Haplotype Reference Consortium and the 1000 Genomes Project data in unrelated 2812 vitiligo cases and 37\u2009079 controls genotyped genome wide, achieving high-quality imputation from markers with minor allele frequency (MAF) as low as 0.0001. Heritability estimated by both approaches was exceedingly high; h2FAM\u2009=\u20090.75\u20130.83 and h2SNP\u2009=\u20090.78. These estimates are statistically identical, indicating there is essentially no remaining \u2018missing heritability\u2019 for vitiligo. Overall, ~70% of h2SNP is represented by common variants (MAF\u2009&amp;gt;\u20090.01) and 30% by rare variants. These results demonstrate that essentially all vitiligo heritable risk is captured by array-based genotyping and deep imputation. These findings suggest that vitiligo may provide a particularly tractable model for investigation of complex disease genetic architecture and predictive aspects of personalized medicine.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa005","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T04:19:00Z","timestamp":1578543540000},"page":"859-863","source":"Crossref","is-referenced-by-count":24,"title":["Deep genotype imputation captures virtually all heritability of autoimmune vitiligo"],"prefix":"10.1093","volume":"29","author":[{"given":"Genevieve H L","family":"Roberts","sequence":"first","affiliation":[{"name":"Human Medical Genetics and Genomics Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A","family":"Santorico","sequence":"first","affiliation":[{"name":"Human Medical Genetics and Genomics Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Mathematical and Statistical Sciences, University of Colorado Denver, Denver, CO 80217, USA"},{"name":"Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, CO 80045, USA"},{"name":"Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Spritz","sequence":"first","affiliation":[{"name":"Human Medical Genetics and Genomics Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"2020033008550224700_ref1","doi-asserted-by":"publisher","first-page":"e0163806","DOI":"10.1371\/journal.pone.0163806","article-title":"The prevalence of vitiligo: a meta-analysis","volume":"11","author":"Zhang","year":"2016","journal-title":"PLoS ONE"},{"key":"2020033008550224700_ref2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470015902.a0026934","volume-title":"eLS","author":"Roberts","year":"2018"},{"key":"2020033008550224700_ref3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/gepi.1370020303","article-title":"Studies on vitiligo. II. Familial aggregation and genetics","volume":"2","author":"Das","year":"1985","journal-title":"Genet. Epidemiol."},{"key":"2020033008550224700_ref4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jaad.2003.12.044","article-title":"Characteristics of genetic epidemiology and genetic models for vitiligo","volume":"51","author":"Zhang","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"2020033008550224700_ref5","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2340\/0001555563249251","article-title":"The genetics of vitiligo","volume":"63","author":"Hafez","year":"1983","journal-title":"Acta Derm. Venereol."},{"key":"2020033008550224700_ref6","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s00439-002-0687-5","article-title":"Vitiligo: complex segregation and linkage disequilibrium analyses with respect to microsatellite loci spanning the HLA","volume":"110","author":"Arcos-Burgos","year":"2002","journal-title":"Hum. Genet."},{"key":"2020033008550224700_ref7","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-62960-5","volume-title":"Vitiligo","author":"Picardo","year":"2019"},{"key":"2020033008550224700_ref8","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1034\/j.1600-0749.2003.00032.x","article-title":"Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families","volume":"16","author":"Alkhateeb","year":"2003","journal-title":"Pigment Cell Res."},{"key":"2020033008550224700_ref9","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1056\/NEJMoa0908547","article-title":"Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo","volume":"362","author":"Jin","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2020033008550224700_ref10","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/ng.2272","article-title":"Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo","volume":"44","author":"Jin","year":"2012","journal-title":"Nat. Genet."},{"key":"2020033008550224700_ref11","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1038\/ng.3680","article-title":"Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants","volume":"48","author":"Jin","year":"2016","journal-title":"Nat. Genet."},{"key":"2020033008550224700_ref12","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":"2020033008550224700_ref13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Thousand Genomes Project Consortium","year":"2015","journal-title":"Nature"},{"key":"2020033008550224700_ref14","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/ng.3679","article-title":"Reference-based phasing using the haplotype reference consortium panel","volume":"48","author":"Loh","year":"2016","journal-title":"Nat. Genet."},{"key":"2020033008550224700_ref15","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1093\/bioinformatics\/btu014","article-title":"Efficient haplotype matching and storage using the positional burrows-wheeler transform (PBWT)","volume":"30","author":"Durbin","year":"2014","journal-title":"Bioinformatics"},{"key":"2020033008550224700_ref16","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"2020033008550224700_ref17","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/ng.3390","article-title":"Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index","volume":"47","author":"Yang","year":"2015","journal-title":"Nat. Genet."},{"key":"2020033008550224700_ref18","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41588-018-0108-x","article-title":"Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits","volume":"50","author":"Evans","year":"2018","journal-title":"Nat. Genet."},{"key":"2020033008550224700_ref19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","article-title":"GCTA: a tool for genome-wide complex trait analysis","volume":"88","author":"Yang","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"2020033008550224700_ref20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nrg3377","article-title":"The heritability of human disease: estimation, uses and abuses","volume":"14","author":"Tenesa","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"2020033008550224700_ref21","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ajhg.2019.06.013","article-title":"Family clustering of autoimmune vitiligo results principally from polygenic inheritance of common risk alleles","volume":"105","author":"Roberts","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"2020033008550224700_ref22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41467-019-08337-4","article-title":"Early-onset autoimmune vitiligo associated with an enhancer variant haplotype that upregulates class II HLA expression","volume":"10","author":"Jin","year":"2019","journal-title":"Nat. Commun."},{"key":"2020033008550224700_ref23","article-title":"Recovery of trait heritability from whole genome sequence data","author":"Wainschtein","year":"2019","journal-title":"bioRxiv"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddaa005\/32451875\/ddaa005.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/29\/5\/859\/32972395\/ddaa005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/hmg\/article-pdf\/29\/5\/859\/32972395\/ddaa005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T21:51:52Z","timestamp":1695592312000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/29\/5\/859\/5704974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,15]]},"references-count":23,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,1,15]]},"published-print":{"date-parts":[[2020,3,27]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddaa005","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,3,1]]},"published":{"date-parts":[[2020,1,15]]}}}