Opin vísindi

Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis

Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis

Title: Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis
Author: Stacey, Simon N.
Zink, Florian
Halldórsson, Gísli Hreinn
Stefánsdóttir, Lilja
Guðjónsson, Sigurjón Axel
Einarsson, Gudmundur
Hjörleifsson, Grimur
Eiríksdóttir, Þjóðbjörg
Helgadottir, Anna
Björnsdottir, Gyda
... 21 more authors Show all authors
Date: 2023-11-06
Language: English
Scope: 6386185
University/Institute: Landspitali - The National University Hospital of Iceland
School: Health Sciences
Department: Faculty of Industrial Engineering, Mechanical Engineering and Computer Science
Faculty of Medicine
Faculty of Sociology, Anthropology and Folkloristics
Faculty of Electrical and Computer Engineering
Series: Nature Genetics; ()
ISSN: 1061-4036
DOI: 10.1038/s41588-023-01555-z
Subject: Náttúrufræðingar; Blóðlæknisfræði; Genetics
URI: https://hdl.handle.net/20.500.11815/4551

Show full item record


Stacey , S N , Zink , F , Halldórsson , G H , Stefánsdóttir , L , Guðjónsson , S A , Einarsson , G , Hjörleifsson , G , Eiríksdóttir , Þ , Helgadottir , A , Björnsdottir , G , Thorgeirsson , T E , Ólafsdóttir , Þ Á , Jónsdóttir , I , Gretarsdottir , S , Tragante , V , Magnússon , M K , Jonsson , H , Gudmundsson , J , Olafsson , S , Holm , H , Gudbjartsson , D F , Sulem , P , Helgason , A S , Þorsteinsdóttir , U , Tryggvadottir , L , Rafnar , T , Melsted , P , Úlfarsson , M Ö , Viðarsson , B , Thorleifsson , G & Stefánsson , K 2023 , ' Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis ' , Nature Genetics . https://doi.org/10.1038/s41588-023-01555-z


Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single hematopoietic stem cell lineage. Using whole-genome sequencing of 45,510 Icelandic and 130,709 UK Biobank participants combined with a mutational barcode method, we identified 16,306 people with CH. Prevalence approaches 50% in elderly participants. Smoking demonstrates a dosage-dependent impact on risk of CH. CH associates with several smoking-related diseases. Contrary to published claims, we find no evidence that CH is associated with cardiovascular disease. We provide evidence that CH is driven by genes that are commonly mutated in myeloid neoplasia and implicate several new driver genes. The presence and nature of a driver mutation alters the risk profile for hematological disorders. Nevertheless, most CH cases have no known driver mutations. A CH genome-wide association study identified 25 loci, including 19 not implicated previously in CH. Splicing, protein and expression quantitative trait loci were identified for CD164 and TCL1A.


Publisher Copyright: © 2023, The Author(s).

Files in this item

This item appears in the following Collection(s)