Language
English
Publication Date
3-1-2025
Journal
Nature Genetics
DOI
10.1038/s41588-025-02085-6
PMID
39948438
PMCID
PMC11906367
PubMedCentral® Posted Date
2-13-2025
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Humans, Prospective Studies, Mexico, Clonal Hematopoiesis, United Kingdom, Genome-Wide Association Study, Female, Biological Specimen Banks, Male, Middle Aged, Polymorphism, Single Nucleotide, DNA Methyltransferase 3A, White People, Aged, DNA (Cytosine-5-)-Methyltransferases, UK Biobank, Population genetics, Haematological cancer, Disease prevention
Published Open-Access
yes
Recommended Citation
Nag, Abhishek; Tachmazidou, Ioanna; Deevi, Sri V V; et al., "Comparative Analysis of the Mexico City Prospective Study and the UK Biobank Identifies Ancestry-Specific Effects on Clonal Hematopoiesis" (2025). Faculty, Staff and Students Publications. 8553.
https://digitalcommons.library.tmc.edu/baylor_docs/8553