“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 Asgeirsdottir, Sverrir 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, Gudmar Thorleifsson, Frosti Jonsson, Pall Melsted, Ingileif Jonsdottir, Thorunn Rafnar, Hilma Holm, Hreinn Stefansson, Jona Saemundsdottir, Daniel F. Gudbjartsson, Olafur T. Magnusson, Gisli Masson, Unnur Thorsteinsdottir, Agnar Helgason, Hakon Jonsson, Patrick Sulem, Kari Stefansson2021-11-17 (, ; similar)⁠:

We describe the analysis of whole genome sequencing (WGS) of 150,119 individuals from the UK biobank (UKB). This yielded a set of high quality variants, including 585,040,410 SNPs, representing 7.0% of all possible human SNPs, and 58,707,036 indels. The large set of variants allows us to characterize selection based on sequence variation within a population through a Depletion Rank (DR) score for windows along the genome. DR analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation.

We define 3 cohorts within the UKB, a large British Irish cohort (XBI) and smaller African (XAF) and South Asian (XSA) cohorts. A haplotype reference panel is provided that allows reliable imputation of most variants carried by 3 or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large scale WGS studies.

Using this formidable new resource, we provide several noteworthy examples of trait associations with rare variants with large effects not found previously through studies based on exome sequencing and/or imputation.