| Title: | Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis |
| Journal: | Nature Genetics |
| Published: | 6 Nov 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37932435/ |
| DOI: | https://doi.org/10.1038/s41588-023-01555-z |
| URL: | https://www.nature.com/articles/s41588-023-01555-z.pdf |
Publication 8381
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Abstract
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.</p>
31 Authors
- Simon N. Stacey
- Florian Zink
- Gisli H. Halldorsson
- Lilja Stefansdottir
- Sigurjon A. Gudjonsson
- Gudmundur Einarsson
- Grimur Hjörleifsson
- Thjodbjorg Eiriksdottir
- Anna Helgadottir
- Gyda Björnsdottir
- Thorgeir E. Thorgeirsson
- Thorunn A. Olafsdottir
- Ingileif Jonsdottir
- Solveig Gretarsdottir
- Vinicius Tragante
- Magnus K. Magnusson
- Hakon Jonsson
- Julius Gudmundsson
- Sigurgeir Olafsson
- Hilma Holm
- Daniel F. Gudbjartsson
- Patrick Sulem
- Agnar Helgason
- Unnur Thorsteinsdottir
- Laufey Tryggvadottir
- Thorunn Rafnar
- Pall Melsted
- Magnus Ö. Ulfarsson
- Brynjar Vidarsson
- Gudmar Thorleifsson
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 56270 | Evaluating and comparing sequence variant associations between the deCODE and UK Biobank datasets across a range of human traits |
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