Mendelian Randomization Study Suggests Causal Relationship Between IBD, Psoriasis

A study published in Frontiers in Immunology found that there appeared to be a causal relationship between inflammatory bowel disease (IBD) and psoriasis. The study, which used a Mendelian randomization approach, also found that psoriasis and psoriatic arthritis (PsA) were associated with Crohn disease (CD).

Genome-wide association studies (GWAS) were searched and extracted from databases including GWAS Catalog, IEU openGWAS, and NealELab. The study population was made up entirely of patients with European ancestry to reduce bias caused by ethnically related confounding factors.

The FinnGen Biobank Analysis Consortium 2021 was also used to identify genetic risk variants for psoriasis and included 4510 cases plus a control group of 212,242 patients. The European Bioinformatics Institute database was used and included 25,042 cases with an IBD diagnosis and 34,915 control patients. Databases with 12,366 cases of ulcerative colitis (UC) with 33,609 controls and 12,194 cases of CD with 28,072 controls were also used.

The primary MR analysis found that genetically predicted IBD was positively associated with psoriasis (odds ratio [OR], 1.1268; 95% CI, 1.0662-1.1908) and the finding was supported by the MR-PRESSO analysis (OR, 1.1271; 95% CI, 1.0708-1.1864).

There was no direct causal effect of psoriasis on IBD in the MR-Egger regression model but the data did suggest significance (OR, 1.1614; 95% CI, 1.0357-1.3022). However, the association was not significant when outliers were removed.

A significant association was also found between total IBD and PsA (OR, 1.1217; 95% CI, 1.0047-1.2043) but none found between total IBD and psoriasis vulgaris. An MR pleiotropy residual sum and outlier (MR-PRESSO) analysis confirmed the association between IBD and PsA (OR, 1.1202; 95% CI, 1.0491-1.1961).

CD had a causal association with total psoriasis (OR, 1.573; 95% CI, 1.0728-1.2485) and with PsA (OR, 1.1431; 95% CI, 1.0415-1.2545), but not with psoriasis vulgaris. The MR-PRESSO analysis confirmed these results by identifying an association between CD and psoriasis (OR, 1.552; 95% CI, 1.0955-1.2182) and CD and PsA (OR, 1.1407; 95% CI, 1.0535-1.2350).

Psoriasis demonstrated a significant association with CD (OR, 1.2689; 95% CI, 1.1504-1.3996) and the association remained significant after 2 outliers were removed (OR, 1.224; 95% CI, 1.1710-1.2760). There was no causal effect of psoriasis on UC.

Although the inverse variance weighted model did not demonstrate a causal effect of PsA on IBD, the MR-PRESSO model identified a causal effect of PsA on IBD (OR, 1.0716; 95% CI, 1.0292-1.1157) and suggested a causal effect of PsA on CD (OR, 1.0667; 95% CI, 1.0194-1.1162).

There were some limitations to this study. A lower P threshold was chosen for evaluating IBD with PsA and psoriasis vulgaris. The investigators’ negative result when evaluating the risk of weak instrument bias should be taken with caution. The sample size of patients with psoriasis vulgaris was small, and the study evaluated people of European ancestry and so cannot be generalized to other races. Finally, the impact of horizontal pleiotropy could not be avoided as the biological function of some genetic variants is not yet known.

The researchers concluded that a causal impact of IBD on psoriasis, especially for PsA, could be assumed. Total psoriasis and PsA were also found to have an association with CD.

“Understanding that specific types of psoriasis and IBD constitute mutual risk factors facilitates early diagnosis enabling more efficient targeting of therapy,” the authors wrote. “Further study is required to elucidate the pathophysiology of the causal relationship between IBD and psoriasis.”

Reference

Li Y, Guo J, Cao Z, Wu J. Causal association between inflammatory bowel disease and psoriasis: a two-sample bidirectional Mendelian randomization study. Front Immunol. 2022;13:916645. doi:10.3389/fimmu.2022.916645