Clonal haematopoiesis subtypes confer dose-dependent risk of serious bacterial infection
Abstract
Clonal haematopoiesis (CH) arises from somatic mutations in haematopoietic stem cells that drive clonal expansion and increase haematological malignancy risk. Here we show that CH confers mutation- and dose-dependent risk of serious bacterial infection (SBI). Using a multi-parameter somatic variant calling and filtering approach, we identified 19,822 mutations across 43 CH genes in 40,560 of 590,537 individuals from three population cohorts (6.87%), validated in a combined analysis of 889,215 individuals. CH was associated with SBI development (HR = 1.22, P = 4.66 × 10⁻²⁹) and 28-day post-infection mortality (RR = 1.84, P = 0.0012), independent of malignancy and robust to adjustment for inflammatory comorbidities and ancestry. Recurrent mutations in SRSF2, DNMT3A, SF3B1, IDH2, and NRAS (n = 2143) conferred substantial absolute risks: 22–25% of individuals with expanded SRSF2 P95 clones developed SBI within 10 years. These associations were consistent across diverse populations and largely independent of bacterial strain.
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BibTeX
@article{fewings2026clonal,
title = {{Clonal haematopoiesis subtypes confer dose-dependent risk of serious bacterial infection}},
author = {Eleanor Fewings and Zhi Yu and Jacob C. Gutierrez and Buu Truong and Petko P. Fiziev and Jeremy McRae and Jeremy Schwartzentruber and Alexander G. Bick and Pradeep Natarajan and Caleb A. Lareau and Jacob C. Ulirsch and Kyle Kai-How Farh},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-77934-x},
url = {https://www.nature.com/articles/s41467-026-77934-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Clonal haematopoiesis subtypes confer dose-dependent risk of serious bacterial infection
AU - Eleanor Fewings
AU - Zhi Yu
AU - Jacob C. Gutierrez
AU - Buu Truong
AU - Petko P. Fiziev
AU - Jeremy McRae
AU - Jeremy Schwartzentruber
AU - Alexander G. Bick
AU - Pradeep Natarajan
AU - Caleb A. Lareau
AU - Jacob C. Ulirsch
AU - Kyle Kai-How Farh
PY - 2026
DA - 2026/10/07
JO - Nature Communications
DO - 10.1038/s41467-026-77934-x
UR - https://www.nature.com/articles/s41467-026-77934-x
AB - Clonal haematopoiesis (CH) arises from somatic mutations in haematopoietic stem cells that drive clonal expansion and increase haematological malignancy risk. Here we show that CH confers mutation- and dose-dependent risk of serious bacterial infection (SBI). Using a multi-parameter somatic variant calling and filtering approach, we identified 19,822 mutations across 43 CH genes in 40,560 of 590,537 individuals from three population cohorts (6.87%), validated in a combined analysis of 889,215 individuals. CH was associated with SBI development (HR = 1.22, P = 4.66 × 10⁻²⁹) and 28-day post-infection mortality (RR = 1.84, P = 0.0012), independent of malignancy and robust to adjustment for inflammatory comorbidities and ancestry. Recurrent mutations in SRSF2, DNMT3A, SF3B1, IDH2, and NRAS (n = 2143) conferred substantial absolute risks: 22–25% of individuals with expanded SRSF2 P95 clones developed SBI within 10 years. These associations were consistent across diverse populations and largely independent of bacterial strain.
SN - 2041-1723
ER -