Mendelian Randomization Analysis Reveals Causal Associations of Inflammatory Bowel Disease with Spondylarthritis

Inflammatory bowel disease (IBD) is strongly associated with Spondylarthritis (SpA), but the causal relationship remains unclear. This study explores the causal associations between IBD (Crohn’s disease [CD] and ulcerative colitis [UC]) and several common subtypes of SpA (Ankylosing Spondylitis [AS], Psoriatic Arthritis [PsA], and Reactive Arthritis [ReA]), using bidirectional two-sample Mendelian randomization (TSMR). The causal effects of genetically predicted IBD on AS, PsA, and ReA were firstly investigated in this forward study. The causal effects from AS, PsA, and ReA on IBD were analyzed in the reverse MR. Inverse variance weighted , weighted median , and MR-Egger were applied in the MR analyses. The pleiotropic effects, heterogeneity, and leave-one-out sensitivity analysis were also evaluated. The forward MR analysis demonstrated that IBD increased risk for AS (OR:1.278; P=1.273× 10–5), PsA (OR:1.192; P= 1.690× 10–5), and ReA (OR:1.106; P =1.524 × 10–3). Among them, CD increased risk of AS (OR:1.196; P=3.424× 10–4), PsA (OR:1.101; P= 1.537× 10–3), ReA (OR:1.079; P = 6.321× 10–3) whereas UC increased risk of AS (OR:1.166; P=2.727× 10–2), PsA (OR:1.110; P= 1.944× 10–2), and ReA (OR:1.091; P =1.768× 10–2). The reverse-direction MR disclosed no notable association; neither was any evidence of pleiotropy detected. Our study verifies a causal effect of IBD to AS, PsA as well as ReA, but not vice versa. This might bring new insights for the management of IBD and SpA in clinical practice.