Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study

Abstract

BackgroundPrevious observational studies have found an association between inflammatory bowel disease (IBD) and psoriasis. Using the mendelian randomization (MR) approach, we aim to determine whether there was a causal association between IBD and psoriasis.MethodsWe performed a two-sample MR with the genetic instruments identified for IBD and its main subtypes, Crohn’s disease (CD) and ulcerative colitis (UC), from a genome-wide association study (GWAS) involving 25,042 cases with an IBD diagnosis and 34,915 controls. Summarized data for psoriasis were obtained from different GWAS studies which included 4510 cases and 212,242 controls without psoriasis. Causal estimates are presented as odds ratios (ORs) with 95% confidence intervals (CIs).ResultsThe overall outcome of MR analysis was to demonstrate that genetic predisposition to IBD was associated with an increased risk of psoriasis (OR: 1.1271; 95% CI: 1.0708 to 1.1864). Psoriatic arthritis (PsA) had a significant association with total IBD (OR: 1.1202; 95% CI: 1.0491 to 1.1961). Casual relationship was also identified for CD-psoriasis (OR: 1.1552; 95% CI: 1.0955 to 1.2182) and CD-PsA (OR: 1.1407; 95% CI: 1.0535 to 1.2350). The bidirectional analysis did not demonstrate that a genetic predisposition to psoriasis was associated with total IBD, although psoriasis showed association with CD (OR: 1.2224; 95% CI: 1.1710 to 1.2760) but not with UC. A genetic predisposition to PsA had a borderline association with IBD (OR: 1.0716; 95% CI: 1.0292 to 1.1157) and a suggestive association with CD (OR: 1.0667; 95% CI: 1.0194 to 1.1162).ConclusionThere appears to be a causal relationship between IBD and psoriasis, especially for PsA, but for psoriasis and IBD, only total psoriasis and PsA were associated with CD. Understanding that specific types of psoriasis and IBD constitute mutual risk factors facilitates the clinical management of two diseases.

Non-alcoholic fatty liver disease is not a causal risk factor for psoriasis: A Mendelian randomization study of 108,835 individuals

“…To avoid this, we also used the MR approach. This approach, described as the "natural randomized controlled trial", is an alternative when randomized controlled trials are unethical or unfeasible and MR studies in medical science, including in the field of psoriasis (36)(37)(38)(39)(40)(41), are increasing (42,43). The present MR results are in agreement with a recent two-sample bidirectional MR study by Zhao et al, investigating causal directions of several comorbidities with psoriasis and psoriasis arthritis (44) without finding a causal association between NAFLD and psoriasis.…”

The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases

“…Since our results seem to be interesting in the literature there are a few studies which present similar results. Yajia et al have presented another MR analysis which confirms the bidirectional relationship between psoriasis, psoriatic arthritis, and CD 50 . However, findings of Dennis' study only support a unidirectional causal effect between CD and psoriasis as well as psoriatic arthritis 51 .…”

Smoking is an independent but not a causal risk factor for moderate to severe psoriasis: A Mendelian randomization study of 105,912 individuals

“…The MR study mimics the randomized controlled trial by using genetic variants as robust proxies for modifiable exposures (Figure 1). The use of MR studies in medical science is increasing (13, 36), also in the field of psoriasis (37)(38)(39)(40)(41)(42). Recently, two studies reported that smoking was a causal risk factor for psoriasis (38, 43), which we could not confirm.…”