Risk factors of clonal hematopoiesis of indeterminate potential.

BACKGROUND: Accumulating evidence demonstrates associations between clonal hematopoiesis of indeterminate potential (CHIP) and increased risks of hematological and non-hematological health outcomes. Although adverse health consequences of CHIP have become well-documented, large knowledge gaps exist regarding the etiology of CHIP. OBJECTIVE: To investigate risk factors for CHIP using large-scale phenotypic data and Mendelian randomization analysis. METHODS: We utilized rich phenotypic and genomic data from the UK Biobank (UKB) to perform a cross-sectional study to systematically investigate risk factors of CHIP, including around 460,000 participants recruited from 2006 to 2010. We used Logistic regression to estimate odds ratios (ORs) of CHIP in relation to risk factors (sociodemographic factors, lifestyle factors, history of diseases, blood cell count, blood biochemistry parameters, proteomics biomarkers and metabolomics biomarkers). In addition, we conducted Mendelian Randomization (MR) analyses to assess causality between the studied risk factors and CHIP, using publicly available summary statistics of genome-wide association studies (GWAS). RESULTS: We found that advanced age, smoking, history of several diseases (including breast cancer and leiomyoma of uterus), as well as several serum biomarkers (monocyte count, proteins LY75, SIGLEC6, SIRPB1 and CYB5R2) were associated with CHIP. CONCLUSION: Our findings expanded existing knowledge base by demonstrating novel risk factors of CHIP, especially history of several diseases and serum biomarkers. These findings advance understanding of the etiology of CHIP.