Browsing by Author "Hasan, A K Rafeul"

Clonal hematopoiesis is characterized by the accumulation of blood cells originating from a single mutated hematopoietic stem cell clone. Clonal hematopoiesis has been hypothesized to contribute to systemic inflammation, and by doing so increase the risk for inflammatory diseases. Despite the growing body of evidence from clinical datasets and murine levels linking clonal hematopoiesis and inflammation, the causative role of clonal hematopoiesis in promoting inflammation remains to be fully elucidated. The primary goal of this master's thesis is to investigate the potential causative relationship between clonal hematopoiesis (CH) and rheumatoid arthritis, one of the most common autoimmune diseases previously associated with clonal hematopoiesis. The analysis is done primarily by employing Mendelian randomization (MR) and multivariate logistic regression analyses to perform two-sample Mendelian randomization in a bidirectional manner to assess the strength of the analysis along with exploring potential pleiotropy. We leverage data from two large population-level cohorts: the FinnGen study and the UK Biobank project. We also employed multivariate logistic regression to validate the instrumental variables of the UK Biobank within the FinnGen data. Despite prior epidemiological and functional literature linking clonal hematopoiesis and rheumatoid arthritis, we observed no association between these two in these large-scale Mendelian randomization analyses. This may be due to differences in cohort characteristics and detection methods for clonal hematopoiesis between the two cohorts. The thesis discusses the strengths and weaknesses of Mendelian randomization in evaluating causative links between human phenotypes. This work contributes to the growing area of research on the genetic determinants of inflammatory diseases and opens avenues for further research into the role of CH in disease pathogenesis