作者
Joshua S Weinstock, Jayakrishnan Gopakumar, Bala Bharathi Burugula, Md Mesbah Uddin, Nikolaus Jahn, Julia A Belk, Hind Bouzid, Bence Daniel, Zhuang Miao, Nghi Ly, Taralynn M Mack, Sofia E Luna, Katherine P Prothro, Shaneice R Mitchell, Cecelia A Laurie, Jai G Broome, Kent D Taylor, Xiuqing Guo, Moritz F Sinner, Aenne S von Falkenhausen, Stefan Kääb, Alan R Shuldiner, Jeffrey R O’Connell, Joshua P Lewis, Eric Boerwinkle, Kathleen C Barnes, Nathalie Chami, Eimear E Kenny, Ruth JF Loos, Myriam Fornage, Lifang Hou, Donald M Lloyd-Jones, Susan Redline, Brian E Cade, Bruce M Psaty, Joshua C Bis, Jennifer A Brody, Edwin K Silverman, Jeong H Yun, Dandi Qiao, Nicholette D Palmer, Barry I Freedman, Donald W Bowden, Michael H Cho, Dawn L DeMeo, Ramachandran S Vasan, Lisa R Yanek, Lewis C Becker, Sharon LR Kardia, Patricia A Peyser, Jiang He, Michiel Rienstra, Pim Van der Harst, Robert Kaplan, Susan R Heckbert, Nicholas L Smith, Kerri L Wiggins, Donna K Arnett, Marguerite R Irvin, Hemant Tiwari, Michael J Cutler, Stacey Knight, J Brent Muhlestein, Adolfo Correa, Laura M Raffield, Yan Gao, Mariza de Andrade, Jerome I Rotter, Stephen S Rich, Russell P Tracy, Barbara A Konkle, Jill M Johnsen, Marsha M Wheeler, J Gustav Smith, Olle Melander, Peter M Nilsson, Brian S Custer, Ravindranath Duggirala, Joanne E Curran, John Blangero, Stephen McGarvey, L Keoki Williams, Shujie Xiao, Mao Yang, C Charles Gu, Yii-Der Ida Chen, Wen-Jane Lee, Gregory M Marcus, John P Kane, Clive R Pullinger, M Benjamin Shoemaker, Dawood Darbar, Dan M Roden, Christine Albert, Charles Kooperberg, Ying Zhou, JoAnn E Manson, Pinkal Desai, Andrew D Johnson, Rasika A Mathias, Thomas W Blackwell, Goncalo R Abecasis, Albert V Smith, Hyun M Kang, Ansuman T Satpathy, Pradeep Natarajan, Jacob O Kitzman, Eric A Whitsel, Alexander P Reiner, Alexander G Bick, Siddhartha Jaiswal
发表日期
2023/4/27
期刊
Nature
卷号
616
期号
7958
页码范围
755-763
出版商
Nature Publishing Group UK
简介
Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis. These lesions are precursors for blood cancers, , , –, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2 …
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