PLoS ONE (Jan 2020)

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

  • Daniel Svensson,
  • Matilda Rentoft,
  • Anna M Dahlin,
  • Emma Lundholm,
  • Pall I Olason,
  • Andreas Sjödin,
  • Carin Nylander,
  • Beatrice S Melin,
  • Johan Trygg,
  • Erik Johansson

DOI
https://doi.org/10.1371/journal.pone.0237721
Journal volume & issue
Vol. 15, no. 9
p. e0237721

Abstract

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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.