Whole-genome sequencing of 490,640 UK Biobank participants

作者：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 J. 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 T. Lythgow, Peter H. Maccallum, Karyn Mégy, Jonathan Mitchell, Sean M. O’Dell, Amanda O’Neill, Katherine R. Smith, Haeyam Taiy, Menelas N. Pangalos, Ruth E. March, Sebastian Wasilewski, Amgen deCode genetics, Hannes P. Eggertsson, Kristjan H. S. Moore, Hannes Hauswedell, Ögmundur Eiríksson, Aron Skaftason, Nokkvi Gislason, Svanhvít Sigurjónsdóttir, Magnus Orn Ulfarsson, Gunnar Pálsson, Marteinn Thor 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 Þ. Sverrisson, Brynjar Sigurdsson, Sigurjon Axel Gudjonsson, Gunnar Th Sigurdsson, Gisli Hreinn Halldorsson, Garðar Sveinbjörnsson, Unnur Styrkársdóttir, Droplaug N. Magnúsdóttir, Steinunn Snorradóttir, Kari Th. Kristinsson, Emilia Sobech, Gudmar Thorleifsson, Frosti Jónsson, Páll Melsted, Ingileif Jónsdóttir, Þórunn Rafnar, Hilma Hólm, Hreinn Stefánsson, Jona Saemundsdottir, Daniel Fannar Gudbjartsson, 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, John C. Whittaker, Manolis Dermitzakis, Toby Johnson, Jonathan Davitte, Erik Ingelsson, Johnson & Johnson, Julio Molineros, Yanfei Zhang, Alexander H. Li, Evan H. Baugh, Elisabeth E. Mlynarski, Abolfazl Doostparast Torshizi, Gamal A Abdel-Azim, Brian S. Mautz, Karen Y. He, Jingyue Xi, Shirley Nieves‐Rodriguez, Asif Ali Khan, Songjun Xu, Xingjun Liu, Brice A. J. Sarver, Dongnhu T. Truong, Mohamed-Ramzi Temanni, Christopher D. Whelan, Letizia Goretti, Najat S. Khan, Bélen Fraile, Tommaso Mansi, Gunaretnam Rajagopal, Sanger (Velsera Seven Bridges), Shaheen Akhtar, Siobhan Austin-Guest, Robert C. Barber, Daniel M. Barrett, Tristram Bellerby, Adrian Clarke, Richard C. Clark, Maria Gabriella Coppola, Linda Cornwell, Abby Crackett, Joseph Dawson, Callum Day, Alexander Dove, Jillian Durham, Robert B. Fairweather, Marcella Ferrero, Michael Fenton, Howerd Fordham, Audrey Fraser, Paul Trafford Heath, Emily Heron, Gary Hornett, Lena Hughes-Hallett, David Kelly Jackson, A. C. Smith, Adam Laverack, Katharine Law, Steven R. Leonard, Kevin Lewis, Jennifer Liddle, Alice Lindsell, Sally Linsdell, Jamie Lovell, James Mack, Henry Mallalieu, Irfaan Mamun, Ana Monteiro, Leanne Morrow, Barbora Pardubska, A.N. Popov, Lisa Sloper, Jan Squares, Ian Still, Oprah Taylor, Sam Taylor, Jaime M. Tovar Corona, Elliott Trigg, Valerie E. Vancollie, Paul Voak, Danni Weldon, Alan Wells, Eloise Wells, Mia Kim Williams, Sean Wright, Nevena Miletic, Lea Lenhardt Ackovic, Marijeta Slavkovic-Ilic, Mladen Lazarevic, Louise Aigrain, Nicholas M. Redshaw, Michael Andrew Quail, Lesley Shirley, Scott Thurston, Peter Ellis, Laura Grout, Natalie Smerdon, Emma Gray, Richard Rance, Cordelia Langford, UK Biobank, Rory Collins, Mark Effingham, Naomi E. Allen, Jonathan Sellors, Simon Sheard, Mahesh R. Pancholi, Caroline Clark, Lucy Burkitt-Gray, Samantha Welsh, Daniel Fry, R. Watson, Lauren Carson, Alan P Young, Illumina, Rami Mehio, Ole B. Schulz-Trieglaff · 发表于：Nature · 年份：2025 · DOI：10.1038/s41586-025-09272-9 · 被引用次数：129 · 研究领域：Genomics and Rare Diseases、Genetic Associations and Epidemiology、Cancer Genomics and Diagnostics

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.