Integrated analysis of Mendelian Randomization and Bayesian colocalization reveals bidirectional causal association...

Observational studies have suggested an association between inflammatory bowel disease [IBD] and psoriasis. However, the detailed genetic basis, causality, and direction of this association remain unclear.

Bidirectional two-sample Mendelian Randomization [MR] analysis was conducted using summary statistics from published genome-wide association studies. Bayesian Colocalization and multivariable MR [MVMR] analyses were performed to identify candidate variants and risk genes involved in the shared genetic basis between IBD, psoriasis, and their subtypes.

Genetically predicted IBD and Crohn's disease [CD] were associated with an increased risk of psoriasis, psoriasis vulgaris [PsV], and psoriatic arthritis [PsA] (IBD on psoriasis: pooled odds ratio [OR] 1.09, 95% confidence interval [CI] 1.04-1.14, p = .0001; CD on psoriasis: pooled OR 1.10, 95% CI 1.06-1.15, p < .0001) and vice versa (psoriasis on IBD: pooled OR 1.11, 95%CI 1.02-1.21), whereas CD only exhibited a unidirectional association with psoriasis. Colocalization analysis revealed eight candidate genetic variants and risk genes (including LINC00824, CDKAL1, IL10, IL23R, DNAJC27, LPP, RUNX3, and RGS14) associated with a shared genetic basis. Among these, IL23R, DNAJC27, LPP, and RGS14 were further validated by MVMR analysis.

Our findings indicated bidirectional causal associations between IBD and psoriasis (including PsV and PsA), which were attributed primarily to CD rather than Ulcerative colitis [UC]. Furthermore, we identified several candidate variants and risk genes involved in the shared genetic basis of IBD and psoriasis. Acquiring a better understanding of the shared genetic architecture underlying IBD and psoriasis would help improve clinical strategies.