The sequences of 150,119 genomes in the UK Biobank
Bjarni V. Halldórsson, Hannes P. Eggertsson, Kristjan H. S. Moore, Hannes Hauswedell, Ögmundur Eiríksson, Magnús Ö. Úlfarsson, Gunnar Pálsson, Marteinn T. Hardarson, Ásmundur Oddsson, Brynjar Ö. Jensson, Snædís Kristmundsdóttir, Brynja D. Sigurpalsdottir, Ólafur Andri Stefánsson, Doruk Beyter, Guillaume Holley, Vinicius Tragante, Arnaldur Gylfason, Pall I. Olason, Florian Zink, Margret Asgeirsdottir, Sverrir T. Sverrisson, Brynjar Sigurdsson, Sigurjón A. Guðjónsson, Gunnar Sigurðsson, Gísli H. Halldórsson, Garðar Sveinbjörnsson, Kristján Norland, Unnur Styrkársdóttir, Droplaug N. Magnúsdóttir, Steinunn Snorradóttir, Kári Kristinsson, Emilia Sobech, Helgi Jónsson, Árni Jón Geirsson, Ísleifur Ólafsson, Pálmi V. Jónsson, Ole Birger Pedersen, Christian Erikstrup, Søren Brunak, Sisse Rye Ostrowski, Steffen Andersen, Karina Banasik, Kristoffer Sølvsten Burgdorf, Maria Didriksen, Khoa Manh Dinh, Christian Erikstrup, Daníel F. Guðbjartsson, Thomas Folkmann Hansen, Henrik Hjalgrim, Gregor B. E. Jemec, Poul Jennum, Pär I. Johansson, Margit Anita Hørup Larsen, Susan Mikkelsen, Kasper Nielsen, Mette Nyegaard, Sisse Rye Ostrowski, Susanne Gjørup Sækmose, Erik Sørensen, Unnur Þorsteinsdóttir, Mie Topholm Brun, Henrik Ullum, Thomas Werge, Guðmar Þorleifsson, Frosti Jónsson, Páll Melsted, Ingileif Jónsdóttir, Þórunn Rafnar, Hilma Hólm, Hreinn Stefánsson, Jona Saemundsdottir, Daníel F. Guðbjartsson, Ólafur Þ. Magnússon, Gísli Másson, Unnur Þorsteinsdóttir, Agnar Helgason, Hákon Jónsson, Patrick Sulem, Kāri Stefánsson
Abstract
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 data 1,2 . Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank 3 . 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.