| Title: | Shared and distinct genetic etiologies for different types of clonal hematopoiesis |
| Journal: | Nature Communications |
| Published: | 8 Sep 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37684235/ |
| DOI: | https://doi.org/10.1038/s41467-023-41315-5 |
| URL: | https://www.nature.com/articles/s41467-023-41315-5.pdf |
Publication 9605
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Abstract
Clonal hematopoiesis (CH) - age-related expansion of mutated hematopoietic clones - can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes). Co-occurring CH raises questions as to their origin, selection, and impact. We integrate sequence and genotype array data in up to 482,378 UK Biobank participants to demonstrate shared genetic architecture across CH types. Our analysis suggests a cellular evolutionary trade-off between different types of CH, with LOY occurring at lower rates in individuals carrying mutations in established CHIP genes. We observed co-occurrence of CHIP and mCAs with overlap at TET2, DNMT3A, and JAK2, in which CHIP precedes mCA acquisition. Furthermore, individuals carrying overlapping CH had high risk of future lymphoid and myeloid malignancies. Finally, we leverage shared genetic architecture of CH traits to identify 15 novel loci associated with leukemia risk.</p>
15 Authors
- Derek W. Brown
- Liam D. Cato
- Yajie Zhao
- Satish K. Nandakumar
- Erik L. Bao
- Eugene J. Gardner
- Aubrey K. Hubbard
- Alexander DePaulis
- Thomas Rehling
- Lei Song
- Kai Yu
- Stephen J. Chanock
- John R. B. Perry
- Vijay G. Sankaran
- Mitchell J. Machiela
3 Applications
| Application ID | Title |
|---|---|
| 9905 | Using genetics to elucidate the relationship between socioeconomic/behavioural traits and disease |
| 21552 | Detection of large-scale copy-number and copy-neutral mosaic alterations in circulating leukocyte DNA of UK Biobank cancer cases and cancer-free controls |
| 31063 | Methodological extensions to estimate genetic heritability and shared risk factors for phenotypes of the UK Biobank |
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