The sequences of 150,119 genomes in the UK Biobank
Authors: Halldorsson Bjarni V. , Eggertsson Hannes P. , Moore Kristjan H. S. , Hauswedell Hannes , Eiriksson Ogmundur , Ulfarsson Magnus O. , Palsson Gunnar , Hardarson Marteinn T. , Oddsson Asmundur , Jensson Brynjar O. , Kristmundsdottir Snaedis , Sigurpalsdottir Brynja D. , Stefansson Olafur A. , Beyter Doruk , Holley Guillaume , Tragante Vinicius , Gylfason Arnaldur , Olason Pall I. , Zink Florian , Asgeirsdottir Margret , Sverrisson Sverrir T. , Sigurdsson Brynjar , Gudjonsson Sigurjon A. , Sigurdsson Gunnar T. , Halldorsson Gisli H. , Sveinbjornsson Gardar , Norland Kristjan , Styrkarsdottir Unnur , Magnusdottir Droplaug N. , Snorradottir Steinunn , Kristinsson Kari , Sobech Emilia , Jonsson Helgi , Geirsson Arni J. , Olafsson Isleifur , Jonsson Palmi , Pedersen Ole Birger , Erikstrup Christian , Brunak Søren , Ostrowski Sisse Rye ,   DBDS Genetic Consortium, Andersen Steffen , Banasik Karina , Burgdorf Kristoffer , Didriksen Maria , Dinh Khoa Manh , Erikstrup Christian , Gudbjartsson Daniel , Hansen Thomas Folkmann , Hjalgrim Henrik , Jemec Gregor , Jennum Poul , Johansson Pär Ingemar , Larsen Margit Anita Hørup , Mikkelsen Susan , Nielsen Kasper Rene , Nyegaard Mette , Ostrowski Sisse Rye , Sækmose Susanne , Sørensen Erik , Thorsteinsdottir Unnur , Brun Mie Topholm , Ullum Henrik , Werge Thomas , Thorleifsson Gudmar , Jonsson Frosti , Melsted Pall , Jonsdottir Ingileif , Rafnar Thorunn , Holm Hilma , Stefansson Hreinn , Saemundsdottir Jona , Gudbjartsson Daniel F. , Magnusson Olafur T. , Masson Gisli , Thorsteinsdottir Unnur , Helgason Agnar , Jonsson Hakon , Sulem Patrick , Stefansson Kari 
Published: July 2022

AbstractDetailed 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.