Journal article
Comparative analysis of the Mexico City Prospective Study and the UK Biobank identifies ancestry-specific effects on clonal hematopoiesis
- Abstract:
- The impact of genetic ancestry on the development of clonal hematopoiesis (CH) remains largely unexplored. Here, we compared CH in 136,401 participants from the Mexico City Prospective Study (MCPS) to 416,118 individuals from the UK Biobank (UKB) and observed CH to be significantly less common in MCPS compared to UKB (adjusted odds ratio = 0.59, 95% confidence interval (CI) = [0.57, 0.61], P = 7.31 × 10−185). Among MCPS participants, CH frequency was positively correlated with the percentage of European ancestry (adjusted beta = 0.84, 95% CI = [0.66, 1.03], P = 7.35 × 10−19). Genome-wide and exome-wide association analyses in MCPS identified ancestry-specific variants in the TCL1B locus with opposing effects on DNMT3A-CH versus non-DNMT3A-CH. Meta-analysis of MCPS and UKB identified five novel loci associated with CH, including polymorphisms at PARP11/CCND2, MEIS1 and MYCN. Our CH study, the largest in a non-European population to date, demonstrates the power of cross-ancestry comparisons to derive novel insights into CH pathogenesis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 5.2MB, Terms of use)
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- Publisher copy:
- 10.1038/s41588-025-02085-6
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Genetics More from this journal
- Volume:
- 57
- Issue:
- 3
- Pages:
- 572-582
- Publication date:
- 2025-02-13
- Acceptance date:
- 2025-01-09
- DOI:
- EISSN:
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1546-1718
- ISSN:
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1061-4036
- Language:
-
English
- Pubs id:
-
2085986
- Local pid:
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pubs:2085986
- Source identifiers:
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2773683
- Deposit date:
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2025-03-14
- ARK identifier:
Terms of use
- Copyright holder:
- Wen et al
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons. org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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