Dataset Information

Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer.

ABSTRACT:

Background

Some retrospective studies reported that psoriasis (PsO) and psoriatic arthritis (PsA) may have been associated with an elevated risk of skin cancer. The causal associations among them remain unclear.

Objectives

To evaluate the causal association of among both PsO and PsA, and skin cancer.

Methods

We performed large-scale two-sample and Multivariate Mendelian randomization analyses to examine whether there is a causal relationship between PsO and PsA, and skin cancer, encompassing basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM).

Results

Genetically predicted PsO, per log-odds ratio increase, showed no significant association with the risk of BCC, cSCC, and CM. The odds ratios (with corresponding 95% confidence intervals) for BCC, cSCC, and CM were 1.00 (0.99,1.01) (P_Ivw = 0.990), 0.94(0.89, 1.00) (P_Ivw = 0.065), and 0.99 (0.98, 1.01) (P_Ivw = 0.239), respectively. PsA showed a significant association with a decreased risk of BCC, with odds ratios (with corresponding 95% confidence intervals) of 1.00 (1.00, 1.00) (P_Ivw = 0.214) and 1.00 (1.00, 1.00) (P_Ivw = 0.477), respectively. Univariate analysis of the FinnGen database demonstrated PsA did exhibit a significant association with the decrease risk of BCC, with an odds ratio of 0.94(0.90,0.99) (P_Ivw = 0.016). However, this association disappeared after other risk factors were adjusted.

Conclusions

Our findings suggest no causal association between PsO and PsA and the genetic risk of skin cancer. Further observational studies are required to elucidate the relationship among PsO, PsA, and skin cancer.

SUBMITTER: Yu N

PROVIDER: S-EPMC10546308 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer.

Yu Nianzhou N Wang Jiayi J Liu Yuancheng Y Guo Yeye Y

Frontiers in immunology 20230919

<h4>Background</h4>Some retrospective studies reported that psoriasis (PsO) and psoriatic arthritis (PsA) may have been associated with an elevated risk of skin cancer. The causal associations among them remain unclear.<h4>Objectives</h4>To evaluate the causal association of among both PsO and PsA, and skin cancer.<h4>Methods</h4>We performed large-scale two-sample and Multivariate Mendelian randomization analyses to examine whether there is a causal relationship between PsO and PsA, and skin ca ...[more]

PMID: 37795084

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Project description:BackgroundNumerous observational studies have identified associations between both psoriasis (PsO) and psoriatic arthritis (PsA), and autoimmune diseases (AIDs); however, the causality of these associations remains undetermined.MethodsWe conducted a bidirectional two-sample Mendelian Randomization study to identify causal associations and directions between both PsO and PsA and AIDs, such as systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), uveitis, bullous pemphigoid (BP), Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA), vitiligo, and ankylosing spondylitis (AS). The causal inferences were drawn by integrating results from four regression models: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, and Maximum Likelihood. Furthermore, we performed sensitivity analyses to confirm the reliability of our findings.ResultsThe results showed that CD [IVW odds ratio (ORIVW), 1.11; 95% confidence interval (CI), 1.06-1.17; P = 8.40E-06], vitiligo (ORIVW, 1.16; 95% CI, 1.05-1.28; P = 2.45E-03) were risk factors for PsO, while BP may reduce the incidence of PsO (ORIVW, 0.91; 95% CI, 0.87-0.96; P = 1.26E-04). CD (ORIVW, 1.07; 95% CI, 1.02-1.12; P = 0.01), HT (ORIVW, 1.23; 95% CI, 1.08-1.40; P = 1.43E-03), RA (ORIVW, 1.11; 95% CI, 1.02-1.21, P = 2.05E-02), AS (ORIVW, 2.18; 95% CI, 1.46-3.27; P = 1.55E-04), SLE (ORIVW, 1.04; 95% CI, 1.01-1.08; P = 1.07E-02) and vitiligo (ORIVW, 1.27; 95% CI, 1.14-1.42; P = 2.67E-05) were risk factors for PsA. Sensitivity analyses had validated the reliability of the results.ConclusionsOur study provides evidence for potential causal relationships between certain AIDs and both PsO and PsA. Specifically, CD and vitiligo may increase the risk of developing PsO, while CD, HT, SLE, RA, AS, and vitiligo may elevate the risk for PsA. Additionally, it is crucial to closely monitor the condition of PsO patients with specific AIDs, as they have a higher likelihood of developing PsA than those without AIDs. Moving forward, greater attention should be paid to PsA and further exploration of other PsO subtypes is warranted.

Project description:ImportancePsoriasis, psoriatic arthritis, and inflammatory bowel disease, ie, Crohn disease and ulcerative colitis, are chronic systemic immune-mediated disorders affecting an increasing proportion of adults and children worldwide. Observational studies have suggested an association between inflammatory bowel disease and psoriasis and vice versa. So far, however, it remains unclear whether and in which direction causal relationships exist.ObjectiveTo investigate the association between inflammatory bowel disease, particularly Crohn disease and ulcerative colitis, and psoriasis or psoriatic arthritis.Design, setting, and participantsA bidirectional 2-sample mendelian randomization study was conducted using summary statistics from genome-wide association studies including up to 463 372 European individuals. Total and direct effects were derived performing an iterative radial and robust inverse-variance weighted method within the univariable and multivariable mendelian randomization setting, respectively. Causal estimates were verified using a validation inflammatory bowel disease sample, a series of pleiotropy-robust mendelian randomization methods, and sensitivity analyses based on a PhenoScanner search in conjunction with network analysis. Data analysis was performed from April to May 2022.Main outcomes and measuresInflammatory bowel disease, Crohn disease, ulcerative colitis, psoriasis, and psoriatic arthritis were used as both exposures and outcomes.ResultsThe European samples included 12 882 cases of inflammatory bowel disease and 5621 cases of psoriasis. The proportion of women ranged between 48% and 56%. Genetically predicted inflammatory bowel disease was associated with higher risk of psoriasis (pooled odds ratio [OR], 1.10; 95% CI, 1.05-1.15; P < .001) and psoriatic arthritis (pooled OR, 1.10; 95% CI, 1.04-1.18; P = .003). In contrast with ulcerative colitis, the Crohn disease subentity was associated with psoriasis (OR, 1.16; 95% CI, 1.12-1.20; P < .001) and psoriatic arthritis (OR, 1.13; 95% CI, 1.06-1.20; P < .001). Regarding the reverse directions, no notable associations could be found.Conclusions and relevanceFindings of this mendelian randomization study support a causal effect between inflammatory bowel disease and psoriasis as well as psoriatic arthritis, but not vice versa. It seems that especially Crohn disease and not ulcerative colitis is responsible for the causal effect of inflammatory bowel disease on both psoriasis outcomes. These findings have implications for the management of inflammatory bowel disease and psoriasis in clinical practice.

Project description:BackgroundCurrently, there has been observed a significant alteration in the composition of the gut microbiome (GM) and serum metabolites in patients with psoriatic arthritis (PsA) compared to healthy individuals. However, previous observational studies have shown inconsistent results regarding the alteration of gut microbiota/metabolites. In order to shed light on this matter, we utilized Mendelian randomization to determine the causal effect of GM/metabolites on PsA.MethodsWe retrieved summary-level data of GM taxa/metabolites and PsA from publicly available GWAS statistics. Causal relationships between GM/metabolites and PsA were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the robustness of our findings, we conducted sensitivity analyses, multivariable MR analysis (MVMR), and additional analysis including replication verification analysis, LDSC regression, and Steiger test analysis. Furthermore, we investigated reverse causality through a reverse MR analysis. Finally, we conducted an analysis of expression quantitative trait loci (eQTLs) involved in the metabolic pathway to explore potential molecular mechanisms of metabolism.ResultsOur findings reveal that eight GM taxa and twenty-three serum metabolites are causally related to PsA (P < 0.05). Notably, a higher relative abundance of Family Rikenellaceae (ORIVW: 0.622, 95% CI: 0.438-0.883, FDR = 0.045) and elevated serum levels of X-11538 (ORIVW: 0.442, 95% CI: 0.250-0.781, FDR = 0.046) maintain significant causal associations with a reduced risk of PsA, even after adjusting for multiple testing correction and conducting MVMR analysis. These findings suggest that Family Rikenellaceae and X-11538 may have protective effects against PsA. Our sensitivity analysis and additional analysis revealed no significant horizontal pleiotropy, reverse causality, or heterogeneity. The functional enrichment analysis revealed that the eQTLs examined were primarily associated with glycerolipid metabolism and the expression of key metabolic factors influenced by bacterial infections (Vibrio cholerae and Helicobacter pylori) as well as the mTOR signaling pathway.ConclusionIn conclusion, our study demonstrates that Family Rikenellaceae and X-11538 exhibit a strong and negative causal relationship with PsA. These particular GM taxa and metabolites have the potential to serve as innovative biomarkers, offering valuable insights into the treatment and prevention of PsA. Moreover, bacterial infections and mTOR-mediated activation of metabolic factors may play an important role in this process.

Project description:IntroductionPrevious studies have proposed a possible gut-skin axis, and linked gut microbiota to psoriasis risks. However, there is heterogeneity in existing evidence. Observational research is prone to bias, and it is hard to determine causality. Therefore, this study aims to evaluate possible causal associations between gut microbiota (GM) and psoriasis.MethodsWith published large-scale GWAS (genome-wide association study) summary datasets, two-sample Mendelian randomization (MR) was performed to sort out possible causal roles of GM in psoriasis and arthropathic psoriasis (PsA). The inverse variance weighted (IVW) method was taken as the primary evaluation of causal association. As complements to the IVW method, we also applied MR-Egger, weighted median. Sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept test, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) global test, and leave-one-out analysis.ResultsBy primary IVW analysis, we identified nominal protective roles of Bacteroidetes (odds ratio, OR 0.81, P = 0.033) and Prevotella9 (OR 0.87, P = 0.045) in psoriasis risks. Bacteroidia (OR 0.65, P = 0.03), Bacteroidales (OR 0.65, P = 0.03), and Ruminococcaceae UCG002 (OR 0.81, P = 0.038) are nominally associated with lower risks for PsA. On the other hand, Pasteurellales (OR 1.22, P = 0.033), Pasteurellaceae (OR 1.22, P = 0.033), Blautia (OR 1.46, P = 0.014), Methanobrevibacter (OR 1.27, P = 0.026), and Eubacterium fissicatena group (OR 1.21, P = 0.028) are nominal risk factors for PsA. Additionally, E. fissicatena group is a possible risk factor for psoriasis (OR 1.22, P = 0.00018). After false discovery rate (FDR) correction, E. fissicatena group remains a risk factor for psoriasis (PFDR = 0.03798).ConclusionWe comprehensively evaluated possible causal associations of GM with psoriasis and arthropathic psoriasis, and identified several nominal associations. E. fissicatena group remains a risk factor for psoriasis after FDR correction. Our results offer promising therapeutic targets for psoriasis clinical management.

Dataset Information

Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer.

Background

Objectives

Methods

Results

Conclusions

Publications

Multivariate Mendelian randomization provides no evidence for causal associations among both psoriasis and psoriatic arthritis, and skin cancer.

Similar Datasets

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