Whole-genome sequencing of 490,640 UK Biobank participants
Manuscript Writing Group, Keren Carss, Bjarni V. Halldórsson, Liping Hou, Jimmy Z. Liu, Eleanor Wheeler, Yancy Lo, Kousik Kundu, Zhuoyi Huang, Ben Lacey, Ryan S. Dhindsa, Diana Rajan, Jelena Randjelović, Neil Marriott, Carol E. Scott, Ahmet Sinan Yavuz, Ian Johnston, Trevor Howe, Mary Helen Black, Kāri Stefánsson, Robert A. Scott, Slavé Petrovski, Shuwei Li, Adrián Cortés, AstraZeneca, Fengyuan Hu, Quanli Wang, Oliver S. Burren, Sri V. V. Deevi, Carolina Haefliger, Kieren Lythgow, Peter Maccallum, Karyn Mégy, Jonathan Mitchell, Sean M. O’Dell, Amanda O’Neill, Katherine R. Smith, Haeyam Taiy, Menelas N. Pangalos, Ruth March, Sebastian Wasilewski, Amgen deCode genetics, Hannes P. Eggertsson, Kristjan H. S. Moore, Hannes Hauswedell, Ögmundur Eiríksson, Aron Skaftason, Nokkvi Gislason, Svanhvít Sigurjónsdóttir, 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, Unnur Styrkársdóttir, Droplaug N. Magnúsdóttir, Steinunn Snorradóttir, Kári Kristinsson, Emilia Sobech, Gudmar Thorleifsson, Frosti Jónsson, Páll Melsted, Ingileif Jónsdóttir, Þórunn Rafnar, Hilma Hólm, Hreinn Stefánsson, Jona Saemundsdottir, Daníel F. Guðbjartsson, Ólafur Þ. Magnússon, Gísli Másson, Unnur Thorsteinsdottir, Agnar Helgason, Hákon Jónsson, Patrick Sulem, GSK, Jatin Sandhuria, Tom G. Richardson, Laurence J Howe, Chloe Robins, Dongjing Liu, Patrick K. Albers, Mariana Pereira, Daniel D. Seaton, Yurii S. Aulchenko
Abstract
Abstract Whole-genome sequencing provides an unbiased and complete view of the human genome and enables the discovery of genetic variation without the technical limitations of other genotyping technologies. Here we report on whole-genome sequencing of 490,640 UK Biobank participants, building on previous genotyping effort 1 . This advance deepens our understanding of how genetics associates with disease biology and further enhances the value of this open resource for the study of human biology and health. Coupling this dataset with rich phenotypic data, we surveyed within- and cross-ancestry genomic associations and identified novel genetic and clinical insights. Although most associations with disease traits were primarily observed in individuals of European ancestries, strong or novel signals were also identified in individuals of African and Asian ancestries. With the improved ability to accurately genotype structural variants and exonic variation in both coding and UTR sequences, we strengthened and revealed novel insights relative to whole-exome sequencing 2,3 analyses. This dataset, representing a large collection of whole-genome sequencing data that is available to the UK Biobank research community, will enable advances of our understanding of the human genome, facilitate the discovery of diagnostics and therapeutics with higher efficacy and improved safety profile, and enable precision medicine strategies with the potential to improve global health.