The sequences of 150,119 genomes in the UK Biobank

Bjarni V Halldorsson, Hannes P Eggertsson, Kristjan H S Moore, Hannes Hauswedell, Ogmundur Eiriksson, Magnus O Ulfarsson, Gunnar Palsson, Marteinn T Hardarson, Asmundur Oddsson, Brynjar O Jensson, Snaedis Kristmundsdottir, Brynja D Sigurpalsdottir, Olafur A Stefansson, Doruk Beyter, Guillaume Holley, Vinicius Tragante, Arnaldur Gylfason, Pall I Olason, Florian Zink, Margret AsgeirsdottirSverrir T Sverrisson, Brynjar Sigurdsson, Sigurjon A Gudjonsson, Gunnar T Sigurdsson, Gisli H Halldorsson, Gardar Sveinbjornsson, Kristjan Norland, Unnur Styrkarsdottir, Droplaug N Magnusdottir, Steinunn Snorradottir, Kari Kristinsson, Emilia Sobech, Helgi Jonsson, Arni J Geirsson, Isleifur Olafsson, Palmi Jonsson, Ole Birger Pedersen, Christian Erikstrup, Søren Brunak, Sisse Rye Ostrowski, Gudmar Thorleifsson, Frosti Jonsson, Pall Melsted, Ingileif Jonsdottir, Thorunn Rafnar, Hilma Holm, Hreinn Stefansson, Jona Saemundsdottir, Daniel F Gudbjartsson, Olafur T Magnusson, DBDS Genetic Consortium, Mie Topholm Bruun (Member of author group)

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Abstract

Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data1,2. Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank3. This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation.

Original languageEnglish
JournalNature
Volume607
Issue number7920
Pages (from-to)732-740
ISSN0028-0836
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

© 2022. The Author(s).

Keywords

  • Africa/ethnology
  • Asia/ethnology
  • Biological Specimen Banks
  • Cohort Studies
  • Conserved Sequence
  • Databases, Genetic
  • Exons/genetics
  • Genetic Variation
  • Genome, Human/genetics
  • Genomics
  • Haplotypes/genetics
  • Humans
  • INDEL Mutation
  • Ireland/ethnology
  • Microsatellite Repeats
  • Polymorphism, Single Nucleotide/genetics
  • United Kingdom
  • Whole Genome Sequencing

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