细胞体内携带马赛克染色体改变（mCAs）的克隆细胞在老年阶段会发生扩张，这是克隆造血异常的一个表现。识别影响mCAs的生成和扩张的因素是研究mCAs在健康和疾病中的作用的关键。在本文中，我们报道了广泛测量的血清生物标志物及其与mCAs的可能关联，这可能为促进获得和克隆扩张的分子改变提供新的见解。我们在英国生物库的436,784名无癌症参与者中进行了横断面调查，研究了32个广泛测量的血清生物标志物与自体mCAs、马赛克Y染色体丢失（mLOY）和马赛克X染色体丢失（mLOX）之间的关联。mCAs与多种常见的血清生物标志物相关，例如脂质水平、循环性激素、血糖稳态、炎症和免疫功能、维生素和矿物质、肾功能和肝功能。参与者中携带mCAs的生物标志物水平与未携带mCAs的参与者相比，估计相对差异最高可达5%；同时，细胞比例较高的mCAs个体的平均生物标志物值偏离较大。与性激素结合球蛋白、维生素D和总胆固醇相关的多基因得分也与mCAs相关。总体而言，我们观察到与疾病风险有关的常用临床血清生物标志物与mCAs相关，这表明这些疾病涉及的机制可能与mCA的增殖和克隆扩张有关。牛津大学出版社2023年出版。

Age-related clonal expansion of cells harboring mosaic chromosomal alterations (mCAs) is one manifestation of clonal hematopoiesis. Identifying factors that influence the generation and promotion of clonal expansion of mCAs are key to investigate the role of mCAs in health and disease. Herein, we report on widely measured serum biomarkers and their possible association with mCAs, which could provide new insights into molecular alterations that promote acquisition and clonal expansion. We performed a cross-sectional investigation of the association of 32 widely measured serum biomarkers with autosomal mCAs, mosaic loss of the Y chromosome (mLOY) and mosaic loss of the X chromosome (mLOX) in 436 784 cancer-free participants from the UK Biobank. mCAs were associated with a range of commonly measured serum biomarkers such as lipid levels, circulating sex hormones, blood sugar homeostasis, inflammation and immune function, vitamins and minerals, kidney function and liver function. Biomarker levels in participants with mCAs were estimated to differ by up to 5% relative to mCA-free participants, and individuals with higher cell fraction mCAs had greater deviation in mean biomarker values. Polygenic scores associated with sex hormone binding globulin, vitamin D, and total cholesterol were also associated with mCAs. Overall, we observed commonly used clinical serum biomarkers related to disease risk are associated with mCAs, suggesting mechanisms involved in these diseases could be related to mCA proliferation and clonal expansion.Published by Oxford University Press 2023.