Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Division of Hematology and Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA.
Nat Rev Genet. 2021 Sep;22(9):603-617. doi: 10.1038/s41576-021-00356-6. Epub 2021 May 13.
Clonal haematopoiesis (CH) is a common, age-related expansion of blood cells with somatic mutations that is associated with an increased risk of haematological malignancies, cardiovascular disease and all-cause mortality. CH may be caused by point mutations in genes associated with myeloid neoplasms, chromosomal copy number changes and loss of heterozygosity events. How inherited and environmental factors shape the incidence of CH is incompletely understood. Even though the several varieties of CH may have distinct phenotypic consequences, recent research points to an underlying genetic architecture that is highly overlapping. Moreover, there are numerous commonalities between the inherited variation associated with CH and that which has been linked to age-associated biomarkers and diseases. In this Review, we synthesize what is currently known about how inherited variation shapes the risk of CH and how this genetic architecture intersects with the biology of diseases that occur with ageing.
克隆性造血（CH）是一种常见的、与年龄相关的血细胞扩张，伴有体细胞突变，与血液系统恶性肿瘤、心血管疾病和全因死亡率风险增加相关。CH 可能由与髓系肿瘤相关的基因中的点突变、染色体拷贝数变化和杂合性丢失事件引起。遗传和环境因素如何影响 CH 的发病率尚不完全清楚。尽管几种类型的 CH 可能具有不同的表型后果，但最近的研究表明存在高度重叠的潜在遗传结构。此外，与 CH 相关的遗传变异与与年龄相关的生物标志物和疾病相关的遗传变异之间存在许多共性。在这篇综述中，我们综合了目前已知的关于遗传变异如何影响 CH 风险的知识，以及这种遗传结构如何与衰老相关疾病的生物学相互作用。
