Factors Associated with Risk of Clonal Haematopoiesis of Indeterminate Potential: A Systematic Review and Meta-Analysis.

Introduction: Clonal haematopoiesis of indeterminate potential (CHIP) is a risk factor for blood cancers and non-haematological diseases. Understanding factors that lead to CHIP is essential in developing preventive strategies. We aimed to identify factors associated with risk of CHIP through a systemic literature review. Methods: We searched MEDLINE and EMBASE for original studies reporting an age-adjusted risk measure for factors associated with an outcome of incident or prevalent CHIP. Random effects meta-analyses were performed for factors reported in at least three cohorts. Results: From 3305 abstracts, 26 studies were included, ranging from 118 to 239,216 participants. Risk of CHIP was higher in those with hypertension (Odds Ratio [OR] 1.1, 95% confidence interval 1.03-1.16), HIV infection (OR 2.37; 1.68-3.34), and smoking (OR 1.13; 1.10-1.17). The risk of CHIP was lower in those of Asian compared to White ethnicity (OR 0.73; 0.56-0.94). Male sex was not associated with risk of CHIP overall (OR 0.94; 0.86-1.03), but was associated with reduced risk of DNMT3A-CHIP (OR 0.82; 0.78-0.86) and increased risk of ASXL1-CHIP (OR 2.00; 1.76-2.27) or spliceosome-CHIP (OR 2.51; 2.03-3.11). We demonstrated no association between CHIP and diabetes, body mass index, or cardiovascular disease. Conclusion: Our findings highlight the heterogeneity of CHIP, and suggest that factors associated with risk of CHIP differ between genes. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.