A whole-genome sequenced control population in northern Sweden reveals subregional genetic differences

• Main Authors: Daniel Svensson, Matilda Rentoft, Anna M. Dahlin, Emma Lundholm, Pall I. Olason, Andreas Sjödin, Carin Nylander, Beatrice S. Melin, Johan Trygg, Erik Johansson, Ludmila Prokunina-Olsson
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2020
• Subjects: Medicine; R; Science; Q; Northern Sweden
• Online Access: https://doaj.org/article/6257811d142944b5a93dbe0a8ce0be79

The number of national reference populations that are whole-genome sequenced are rapidly increasing. Partly driving this development is the fact that genetic disease studies benefit from knowing the genetic variation typical for the geographical area of interest. A whole-genome sequenced Swedish national reference population (n = 1000) has been recently published but with few samples from northern Sweden. In the present study we have whole-genome sequenced a control population (n = 300) (ACpop) from Västerbotten County, a sparsely populated region in northern Sweden previously shown to be genetically different from southern Sweden. The aggregated variant frequencies within ACpop are publicly available (DOI 10.17044/NBIS/G000005) to function as a basic resource in clinical genetics and for genetic studies. Our analysis of ACpop, representing approximately 0.11% of the population in Västerbotten, indicates the presence of a genetic substructure within the county. Furthermore, a demographic analysis showed that the population from which samples were drawn was to a large extent geographically stationary, a finding that was corroborated in the genetic analysis down to the level of municipalities. Including ACpop in the reference population when imputing unknown variants in a Västerbotten cohort resulted in a strong increase in the number of high-confidence imputed variants (up to 81% for variants with minor allele frequency < 5%). ACpop was initially designed for cancer disease studies, but the genetic structure within the cohort will be of general interest for all genetic disease studies in northern Sweden.