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Sci Rep. 2017 Jul 20;7(1):6079. doi: 10.1038/s41598-017-05445-3.

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

Author information

1
Human Genetics Branch, National Institute of Mental Health Intramural Research Program, Bethesda, MD, 20892, USA. liping.hou@nih.gov.
2
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
3
Institute for Systems Biology, Seattle, WA, 98109, USA.
4
Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
5
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA.
6
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
7
Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, 44106, USA.
8
Department of Anthropology, University of Kansas, Lawrence, KS, 66045, USA.
9
Human Genetics Branch, National Institute of Mental Health Intramural Research Program, Bethesda, MD, 20892, USA. mcmahonf@mail.nih.gov.

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.

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