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Prevalence, predictors, and outcomes of clonal hematopoiesis in individuals aged ≥80 years.

ABSTRACT: Clonal hematopoiesis (CH), characterized by a fraction of peripheral blood cells carrying an acquired genetic variant, emerges with age. Although in general CH is associated with increased mortality and morbidity, no higher risk of death was observed for individuals ≥80 years. Here, we investigated CH in 621 individuals aged ≥80 years from the population-based LifeLines cohort. Sensitive error-corrected sequencing of 27 driver genes at a variant allele frequency ≥1% revealed CH in the majority (62%) of individuals, independent of gender. The observed mutational spectrum was dominated by DNMT3A and TET2 variants, which frequently (29%) displayed multiple mutations per gene. In line with previous results in individuals ≥80 years, the overall presence of CH did not associate with a higher risk of death (hazard ratio, 0.91; 95% confidence interval, 0.70-1.18; P = .48). Being able to assess the causes of death, we observed no difference between individuals with or without CH, except for deaths related to hematological malignancies. Interestingly, comparison of mutational spectra confined to DNMT3A and TET2 vs spectra containing other mutated genes, showed a higher risk of death when mutations other than DNMT3A or TET2 were present (hazard ratio, 1.48; 95% confidence interval, 1.06-2.08; P = .025). Surprisingly, no association of CH with cardiovascular morbidity was found, irrespective of clone size. Further, CH associated with chronic obstructive pulmonary disease. Data on estimated exposure to DNA damaging toxicities (ie, smoking, a history of cancer [as a proxy for previous genotoxic therapy], and job-related pesticide exposure) showed an association with spliceosome and ASXL1 variants, but not with DNMT3A and TET2 variants.

SUBMITTER: van Zeventer IA

PROVIDER: S-EPMC8095141 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSchistosomiasis is a water-based disease that is believed to affect over 200 million people with an estimated 97% of the infections concentrated in Africa. However, these statistics are largely based on population re-adjusted data originally published by Utroska and colleagues more than 20 years ago. Hence, these estimates are outdated due to large-scale preventive chemotherapy programs, improved sanitation, water resources development and management, among other reasons. For planning, coordination, and evaluation of control activities, it is essential to possess reliable schistosomiasis prevalence maps.MethodologyWe analyzed survey data compiled on a newly established open-access global neglected tropical diseases database (i) to create smooth empirical prevalence maps for Schistosoma mansoni and S. haematobium for individuals aged ? 20 years in West Africa, including Cameroon, and (ii) to derive country-specific prevalence estimates. We used Bayesian geostatistical models based on environmental predictors to take into account potential clustering due to common spatially structured exposures. Prediction at unobserved locations was facilitated by joint kriging.Principal findingsOur models revealed that 50.8 million individuals aged ? 20 years in West Africa are infected with either S. mansoni, or S. haematobium, or both species concurrently. The country prevalence estimates ranged between 0.5% (The Gambia) and 37.1% (Liberia) for S. mansoni, and between 17.6% (The Gambia) and 51.6% (Sierra Leone) for S. haematobium. We observed that the combined prevalence for both schistosome species is two-fold lower in Gambia than previously reported, while we found an almost two-fold higher estimate for Liberia (58.3%) than reported before (30.0%). Our predictions are likely to overestimate overall country prevalence, since modeling was based on children and adolescents up to the age of 20 years who are at highest risk of infection.Conclusion/significanceWe present the first empirical estimates for S. mansoni and S. haematobium prevalence at high spatial resolution throughout West Africa. Our prediction maps allow prioritizing of interventions in a spatially explicit manner, and will be useful for monitoring and evaluation of schistosomiasis control programs.

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Prevalence, predictors, and outcomes of clonal hematopoiesis in individuals aged ≥80 years.

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