Causal association between immune cell traits and Ankylosing Spondylitis: A bidirectional Mendelian randomization study

Abstract

Abstract Background: Previous studies have observed a significant association between immune cell traits and Ankylosing spondylitis (AS); however, a causal relationship has not been established. Therefore, we conducted this bidirectional Mendelian randomization study to comprehensively evaluate the intricate interactions between 731 immune cell traitsand AS, aiming to uncover potential causal relationships while enhancing our understanding of disease development. Methods: We retrieved extensive genome-wide association study (GWAS) data from two reputable sources, the IEU open GWAS database and the FinnGen studies, renowned for their extensive genetic information. We performed a bidirectional Mendelian randomization study to investigate the causal relationship between 731 immune cell traits and Ankylosing Spondylitis (AS). Our analysis utilized the Inverse Variance Weighted (IVW) method, along with MR-Egger, Weighted Median, and Weighted Mode. We assessed associations between 731 immune cell traits and AS using odds ratios (OR) and 95% confidence intervals (CI). Finally, we performed tests for horizontal pleiotropy, heterogeneity, and conducted a leave-one-out sensitivity analysis to validate our results. Results: Our research has established that 10 distinct immune cell types significantly contribute to the development of Ankylosing Spondylitis (AS). We identified 3 types of monocytes, 1 type of T cell, 1 type of B cell, and 1 type of granulocyte as risk factors for AS. In contrast, a different group of immune cells, including 1 type of monocyte, 2 types of T cells, and 1 type of B cell, appears to offer protection against the disease. Concerning the onset of AS, its impact on immune traits is evident in the varied expressions across 41 T cell subgroups: 16 subtypes show high expression, while 25 demonstrate low expression. Similarly, in B cells, 3 subtypes are highly expressed, and 4 subtypes are lowly expressed. Likewise, variations in expression were observed in lymphocytes and monocytes, with 3 types of each showing high and low expression, respectively. Moreover, our study reveals a bidirectional causal relationship between the expression of CX3CR1 on CD14+ CD16- monocytes and on monocytes generally, and the occurrence of AS. Conclusion: The goal of this research is dedicated to exploring the bidirectional causal relationship between immune cells traits and Ankylosing Spondylitis (AS). It aims to not only offer new avenues for unraveling the biological mechanisms of AS but also to guide clinical research towards novel investigative directions and to provide fresh clues for the development of new therapeutic approaches.