克隆造血（CH）是一种以血细胞主要源自单一突变造血干细胞为特征的衰老相关疾病，包括造血系统恶性肿瘤和动脉粥样硬化心血管疾病（ASCVD）。尽管CH在老年人中很常见，但其发展的潜在因素大部分尚不清楚。为了解决这个问题，我们对来自4187名“社区中动脉粥样硬化病（ARIC）”研究参与者的8374份血液DNA样本进行了全外显子测序，随访时间中位数为21年。在此期间，735名参与者发生了CH。我们发现，基线年龄、性别和血脂异常明显影响了CH的发生率，而ASCVD和其他传统ASCVD风险因素没有显示出这样的关联。我们的研究还揭示了生殖细胞系遗传变异与CH发生之间的关联，为CH发展中的基因提供了优先级排序。我们全面的长期评估为了解老年人CH的发生因素提供了新的见解。

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.