作者
Michael D Kessler, Amy Damask, Sean O’Keeffe, Nilanjana Banerjee, Dadong Li, Kyoko Watanabe, Anthony Marketta, Michael Van Meter, Stefan Semrau, Julie Horowitz, Jing Tang, Jack A Kosmicki, Veera M Rajagopal, Yuxin Zou, Yariv Houvras, Arkopravo Ghosh, Christopher Gillies, Joelle Mbatchou, Ryan R White, Niek Verweij, Jonas Bovijn, Neelroop N Parikshak, Michelle G LeBlanc, Marcus Jones, Regeneron Genetics Center, GHS-RGC DiscovEHR Collaboration, David J Glass, Luca A Lotta, Michael N Cantor, Gurinder S Atwal, Adam E Locke, Manuel AR Ferreira, Raquel Deering, Charles Paulding, Alan R Shuldiner, Gavin Thurston, Adolfo A Ferrando, Will Salerno, Jeffrey G Reid, John D Overton, Jonathan Marchini, Hyun M Kang, Aris Baras, Gonçalo R Abecasis, Eric Jorgenson
发表日期
2022/12/8
期刊
Nature
卷号
612
期号
7939
页码范围
301-309
出版商
Nature Publishing Group UK
简介
Clonal haematopoiesis involves the expansion of certain blood cell lineages and has been associated with ageing and adverse health outcomes, , , –. Here we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal haematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 24 loci (21 of which are novel) where germline genetic variation influences predisposition to CHIP, including missense variants in the lymphocytic antigen coding gene LY75, which are associated with reduced incidence of CHIP. We also identify novel rare variant associations with clonal haematopoiesis and telomere length. Analysis of 5,041 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID-19 outcomes, cardiovascular disease, haematologic traits, malignancy, smoking, obesity, infection and all-cause …
引用总数