Ankylosing spondylitis and the genetic correlation of extra-articular manifestations: Evidence from bidirectional Mendelian randomization and Bayesian colocalization.

Spondyloarthritis (SpA) encompasses a group of inflammatory joint disorders affecting the spine and joints, including ankylosing spondylitis and nonradiographic axial SpA, exhibiting diverse extra-articular manifestations. Genetic factors, beyond human leukocyte antigen B27, play a significant role in SpA development. Leveraging advanced statistical methods, this study explores bidirectional Mendelian randomization (MR) and Bayesian colocalization to unravel the genetic links between SpA and its extra-articular manifestations. Positive MR analysis indicates causal relationships between ankylosing spondylitis and various extra-articular conditions. Leave-one-out analysis suggests that these effects are not driven by individual single-nucleotide polymorphisms. In reverse MR, potential reverse causal relationships are explored, revealing uveitis, inflammatory bowel disease, and ulcerative colitis as candidates. Colocalization analysis, unfortunately, does not identify shared genetic foundations. In conclusion, seronegative spinal arthritis may lead to myocarditis, atrioventricular block, bronchiectasis, Crohn disease, and coccygeal plexus syndrome, while there is a 2-way causal relationship with uveitis, inflammatory bowel disease, and ulcerative colitis.