TY - JOUR
T1 - The sequences of 150,119 genomes in the UK Biobank
AU - Halldorsson, Bjarni V.
AU - Eggertsson, Hannes P.
AU - Moore, Kristjan H.S.
AU - Hauswedell, Hannes
AU - Eiriksson, Ogmundur
AU - Ulfarsson, Magnus O.
AU - Palsson, Gunnar
AU - Hardarson, Marteinn T.
AU - Oddsson, Asmundur
AU - Jensson, Brynjar O.
AU - Kristmundsdottir, Snaedis
AU - Sigurpalsdottir, Brynja D.
AU - Stefansson, Olafur A.
AU - Beyter, Doruk
AU - Holley, Guillaume
AU - Tragante, Vinicius
AU - Gylfason, Arnaldur
AU - Olason, Pall I.
AU - Zink, Florian
AU - Asgeirsdottir, Margret
AU - Sverrisson, Sverrir T.
AU - Sigurdsson, Brynjar
AU - Gudjonsson, Sigurjon A.
AU - Sigurdsson, Gunnar T.
AU - Halldorsson, Gisli H.
AU - Sveinbjornsson, Gardar
AU - Norland, Kristjan
AU - Styrkarsdottir, Unnur
AU - Magnusdottir, Droplaug N.
AU - Snorradottir, Steinunn
AU - Kristinsson, Kari
AU - Sobech, Emilia
AU - Pedersen, Ole Birger
AU - Brunak, Søren
AU - Ostrowski, Sisse Rye
AU - Banasik, Karina
AU - Burgdorf, Kristoffer
AU - Didriksen, Maria
AU - Hansen, Thomas Folkmann
AU - Hjalgrim, Henrik
AU - Jemec, Gregor
AU - Jennum, Poul
AU - Johansson, Pär Ingemar
AU - Ostrowski, Sisse Rye
AU - Ullum, Henrik
AU - Werge, Thomas
AU - DBDS Genetic Consortium
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41586-022-04965-x
DO - 10.1038/s41586-022-04965-x
M3 - Journal article
C2 - 35859178
AN - SCOPUS:85134541905
VL - 607
JO - Nature
JF - Nature
SN - 0028-0836
ER -