Genetic Risk of Ankylosing Spondylitis and Second-Line Therapy Need in Crohn’s Disease: A Mendelian Randomization Study

Abstract

Background: Crohn’s disease (CD) and Ankylosing Spondylitis (AS) are chronic conditions with overlapping inflammatory pathways. This research investigates the genetic association between AS and the requirement for more aggressive therapeutic interventions in CD, suggesting a likelihood of increased severity in CD progression among individuals diagnosed with AS. Methods: This study utilized two-sample Mendelian randomization (TSMR) to analyze GWAS datasets for AS and CD requiring second-line treatment. Instrumental variables were selected based on single-nucleotide polymorphisms of genome-wide significance. Analytical methods included inverse-variance weighted (IVW), MR Egger, and other MR approaches, alongside sensitivity analysis, to validate the findings. Results: Our results indicated a significant association between AS genetic predisposition and the increased need for second-line treatments in CD. The IVW method showed an Odds Ratio (OR) of 2.16, and MR Egger provided an OR of 2.71, both were statistically significant. This association persisted even after the exclusion of influential outlier SNP rs2517655, confirming the robustness of our findings. Conclusions: This study suggests that genetic factors contributing to AS may influence the progression of CD, potentially necessitating more intensive treatment strategies. These findings underscore the importance of early screening in patients with co-existing AS and CD for tailoring treatment approaches, thus advancing personalized medicine in the management of these complex conditions.