Whole-genome sequencing of 490,640 UK Biobank participants

• 成果类型: Article
• 署名作者: Carss, Keren; Halldorsson, Bjarni V.; Hou, Liping; Liu, Jimmy; Wheeler, Eleanor; Lo, Yancy; Kundu, Kousik; Huang, Zhuoyi; Ben Lacey, Ben; Dhindsa, Ryan S.; Rajan, Diana; Randjelovic, Jelena; Marriott, Neil; Scott, Carol E.; Yavuz, Ahmet Sinan; Johnston, Ian; Howe, Trevor; Black, Mary Helen; Stefansson, Kari; Scott, Robert; Petrovski, Slave; Li, Shuwei; Cortes, Adrian; Hu, Fengyuan; Wang, Quanli; Burren, Oliver S.; Deevi, Sri V. V.; Haefliger, Carolina; Lythgow, Kieren; Maccallum, Peter H.; Megy, Karyn; Mitchell, Jonathan; O'Dell, Sean; O'Neill, Amanda; Smith, Katherine R.; Taiy, Haeyam; Pangalos, Menelas; March, Ruth; Wasilewski, Sebastian; Eggertsson, Hannes P.; Moore, Kristjan H. S.; Hauswedell, Hannes; Eiriksson, Ogmundur; Skaftason, Aron; Gislason, Nokkvi; Sigurjonsdottir, Svanhvit; 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; Styrkarsdottir, Unnur; Magnusdottir, Droplaug N.; Snorradottir, Steinunn; Kristinsson, Kari; Sobech, Emilia; 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; Sandhuria, Jatin; Richardson, Tom G.; Howe, Laurence; Robins, Chloe; Liu, Dongjing; Albers, Patrick; Pereira, Mariana; Seaton, Daniel; Aulchenko, Yury; Whittaker, John; Dermitzakis, Manolis; Johnson, Toby; Davitte, Jonathan; Ingelsson, Erik; Molineros, Julio; Zhang, Yanfei; Li, Alexander H.; Baugh, Evan H.; Mlynarski, Elisabeth; Torshizi, Abolfazl Doostparast; Abdel-Azim, Gamal; Mautz, Brian; He, Karen Y.; Xi, Jingyue; Nieves-Rodriguez, Shirley; Khan, Asif; Xu, Songjun; Liu, Xingjun; Sarver, Brice; Truong, Dongnhu; Temanni, Mohamed-Ramzi; Whelan, Christopher D.; Goretti, Letizia; Khan, Najat; Fraile, Belen; Mansi, Tommaso; Rajagopal, Guna; Akhtar, Shaheen; Austin-Guest, Siobhan; Barber, Robert; Barrett, Daniel; Bellerby, Tristram; Clarke, Adrian; Clark, Richard; Coppola, Maria; Cornwell, Linda; Crackett, Abby; Dawson, Joseph; Day, Callum; Dove, Alexander; Durham, Jillian; Fairweather, Robert; Ferrero, Marcella; Fenton, Michael; Fordham, Howerd; Fraser, Audrey; Heath, Paul; Heron, Emily; Hornett, Gary; Hughes-Hallett, Lena; Jackson, David K.; Jakubowski Smith, Alexander; Laverack, Adam; Law, Katharine; Leonard, Steven R.; Lewis, Kevin; Liddle, Jennifer; Lindsell, Alice; Linsdell, Sally; Lovell, Jamie; Mack, James; Mallalieu, Henry; Mamun, Irfaan; Monteiro, Ana; Morrow, Leanne; Pardubska, Barbora; Popov, Alexandru; Sloper, Lisa; Squares, Jan; Still, Ian; Taylor, Oprah; Taylor, Sam; Tovar Corona, Jaime M.; Trigg, Elliott; Vancollie, Valerie; Voak, Paul; Weldon, Danni; Wells, Alan; Wells, Eloise; Williams, Mia; Wright, Sean; Miletic, Nevena; Lenhardt Ackovic, Lea; Slavkovic-Ilic, Marijeta; Lazarevic, Mladen; Aigrain, Louise; Redshaw, Nicholas; Quail, Michael; Shirley, Lesley; Thurston, Scott; Ellis, Peter; Grout, Laura; Smerdon, Natalie; Gray, Emma; Rance, Richard; Langford, Cordelia; Collins, Rory; Effingham, Mark; Allen, Naomi; Sellors, Jonathan; Sheard, Simon; Pancholi, Mahesh; Clark, Caroline; Burkitt-Gray, Lucy; Welsh, Samantha; Fry, Daniel; Watson, Rachel; Carson, Lauren; Young, Alan; Mehio, Rami; Schulz-Trieglaff, Ole
• 署名单位: AstraZeneca; Reykjavik University; Johnson & Johnson; Janssen Pharmaceuticals; GlaxoSmithKline; Glaxosmithkline USA; Illumina; AstraZeneca; Wellcome Trust Sanger Institute; University of Iceland; GlaxoSmithKline; Glaxosmithkline United Kingdom; GlaxoSmithKline; AstraZeneca; AstraZeneca; University of Iceland; University of Iceland; Johnson & Johnson; Janssen Pharmaceuticals; Johnson & Johnson; Johnson & Johnson USA; Janssen Biotech Inc; Johnson & Johnson; Janssen Pharmaceuticals; Illumina; Illumina; MRC Biostatistics Unit; University of Cambridge
• 刊物名称: Nature
• ISSN/ISSBN: 0028-0939
• DOI: 10.1038/s41586-025-09272-9
• 发表日期: 2025-09-18
• 关键词: associations; mutations; cataract; protein; gene; founder; variant; exome

摘要

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 effort1. 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 sequencing2,3 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.