Long-term longitudinal analysis of 4,187 participants reveals new insights into determinants of incident clonal hematopoiesis

Abstract

Clonal hematopoiesis (CH), characterized by blood cells predominantly originating from a single mutated hematopoietic stem cell, is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CH is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CH. We found that age at baseline, sex, and dyslipidemia significantly influence the incidence of CH, while ASCVD and other traditional risk factors for ASCVD did not exhibit such associations. Our study also revealed associations between germline genetic variants and incident CH, prioritizing genes in CH development. Our comprehensive longitudinal assessment yields novel insights into the factors contributing to incident CH in older adults.

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study

“…49,50 This is consistent with previous studies demonstrating increased levels of IL-6 and IL-1β in Tet2 loss-offunction mouse models. 21,30,51 Moreover, Kim et al 52 reported that DNMT3A mutant macrophages drove bone loss through Irf3-NF-κB (nuclear factor-κB)-mediated IL-20 expression and increased osteoclastogenesis due to the DNMT3A mutations was ameliorated by alendronate or IL-20 neutralization. 52 These evidence indicated that individuals with CHIP mutations, especially TET2 and DNMT3A may benefit from targeted antiinflammatory therapy.…”