A population-specific reference panel empowers genetic studies of Anabaptist populations

Abstract Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer one solution, however population-specific refere...

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Autores principales:	Liping Hou, Rachel L. Kember, Jared C. Roach, Jeffrey R. O’Connell, David W. Craig, Maja Bucan, William K. Scott, Margaret Pericak-Vance, Jonathan L. Haines, Michael H. Crawford, Alan R. Shuldiner, Francis J. McMahon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a8623fc26ce404885a3507e220acdd0
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spelling	oai:doaj.org-article:6a8623fc26ce404885a3507e220acdd02021-12-02T11:53:04ZA population-specific reference panel empowers genetic studies of Anabaptist populations10.1038/s41598-017-05445-32045-2322https://doaj.org/article/6a8623fc26ce404885a3507e220acdd02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05445-3https://doaj.org/toc/2045-2322Abstract Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer one solution, however population-specific reference panels are needed to assure optimal imputation accuracy and allele frequency estimation. Here we report the Anabaptist Genome Reference Panel (AGRP), the first whole-genome catalogue of variants and phased haplotypes in people of Amish and Mennonite ancestry. Based on high-depth whole-genome sequence (WGS) from 265 individuals, the AGRP contains >12 M high-confidence single nucleotide variants and short indels, of which ~12.5% are novel. These Anabaptist-specific variants were more deleterious than variants with comparable frequencies observed in the 1000 Genomes panel. About 43,000 variants showed enriched allele frequencies in AGRP, consistent with drift. When combined with the 1000 Genomes Project reference panel, the AGRP substantially improved imputation, especially for rarer variants. The AGRP is freely available to researchers through an imputation server.Liping HouRachel L. KemberJared C. RoachJeffrey R. O’ConnellDavid W. CraigMaja BucanWilliam K. ScottMargaret Pericak-VanceJonathan L. HainesMichael H. CrawfordAlan R. ShuldinerFrancis J. McMahonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liping Hou Rachel L. Kember Jared C. Roach Jeffrey R. O’Connell David W. Craig Maja Bucan William K. Scott Margaret Pericak-Vance Jonathan L. Haines Michael H. Crawford Alan R. Shuldiner Francis J. McMahon A population-specific reference panel empowers genetic studies of Anabaptist populations
description	Abstract Genotype imputation is a powerful strategy for achieving the large sample sizes required for identification of variants underlying complex phenotypes, but imputation of rare variants remains problematic. Genetically isolated populations offer one solution, however population-specific reference panels are needed to assure optimal imputation accuracy and allele frequency estimation. Here we report the Anabaptist Genome Reference Panel (AGRP), the first whole-genome catalogue of variants and phased haplotypes in people of Amish and Mennonite ancestry. Based on high-depth whole-genome sequence (WGS) from 265 individuals, the AGRP contains >12 M high-confidence single nucleotide variants and short indels, of which ~12.5% are novel. These Anabaptist-specific variants were more deleterious than variants with comparable frequencies observed in the 1000 Genomes panel. About 43,000 variants showed enriched allele frequencies in AGRP, consistent with drift. When combined with the 1000 Genomes Project reference panel, the AGRP substantially improved imputation, especially for rarer variants. The AGRP is freely available to researchers through an imputation server.
format	article
author	Liping Hou Rachel L. Kember Jared C. Roach Jeffrey R. O’Connell David W. Craig Maja Bucan William K. Scott Margaret Pericak-Vance Jonathan L. Haines Michael H. Crawford Alan R. Shuldiner Francis J. McMahon
author_facet	Liping Hou Rachel L. Kember Jared C. Roach Jeffrey R. O’Connell David W. Craig Maja Bucan William K. Scott Margaret Pericak-Vance Jonathan L. Haines Michael H. Crawford Alan R. Shuldiner Francis J. McMahon
author_sort	Liping Hou
title	A population-specific reference panel empowers genetic studies of Anabaptist populations
title_short	A population-specific reference panel empowers genetic studies of Anabaptist populations
title_full	A population-specific reference panel empowers genetic studies of Anabaptist populations
title_fullStr	A population-specific reference panel empowers genetic studies of Anabaptist populations
title_full_unstemmed	A population-specific reference panel empowers genetic studies of Anabaptist populations
title_sort	population-specific reference panel empowers genetic studies of anabaptist populations
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6a8623fc26ce404885a3507e220acdd0
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A population-specific reference panel empowers genetic studies of Anabaptist populations

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