Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: a bidirectional two-sample Mendelian randomization study.

Numerous 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. We 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. The 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. Our 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.

Duan K ，Wang J ，Chen S ，Chen T ，Wang J ，Wang S ，Chen X ... -  《Frontiers in Immunology》

Association between allergic diseases and both psoriasis and psoriatic arthritis: a bidirectional 2-sample Mendelian randomization study.

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863-0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843-0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829-0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996-0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted.

Zhao D ，Wu S ，Wang Y ，Zheng H ，Zhu M ... -  《-》

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases.

Chen C ，Yan S ，Wan B ，Yu Y ，Zeng J ，Tan L ，Lu J ... -  《-》

A bidirectional two-sample Mendelian randomization study to evaluate the relationship between psoriasis and interstitial lung diseases.

Prior observational studies have suggested a potential direct link between psoriasis (PSO) and interstitial lung disease (ILD). Consequently, we applied Mendelian randomization (MR) to further evaluate the bidirectional causal relationships between PSO and its different phenotypes [psoriatic arthritis (PSA)/psoriasis vulgaris (PSV)] and ILD. Data regarding PSO/PSA/PSV and ILD were sourced from publicly accessible genome-wide association studies (GWAS) databases, focusing on European populations. We used five algorithms- MR Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode- to evaluate the causal relationships between PSO/PSA/PSV and ILD, with a primary emphasis on the IVW method. The analysis indicated a potential association between PSA and an elevated risk of ILD [IVW odds ratio (OR): 1.035 (95% CI 1.008, 1.064; P = 0.012)], with no evidence of a direct relationship between total PSO and PSV with ILD. Conversely, no substantial evidence emerged from the reverse MR analysis to suggest that ILD significantly affects total PSO or the specific PSA/PSV phenotypes. Our findings provide genetic evidence supporting the notion that PSA may be a contributory risk factor for ILD. Further investigations are warranted to explore the underlying mechanisms of this potential causal relationship between PSA and ILD.

Yue L ，Yan Y ，Zhao S 《BMC Pulmonary Medicine》

Investigation of the causal association between Parkinson's disease and autoimmune disorders: a bidirectional Mendelian randomization study.

To date, an increasing number of epidemiological evidence has pointed to potential relationships between Parkinson's disease (PD) and various autoimmune diseases (AIDs), however, no definitive conclusions has been drawn about whether PD is causally related to AIDs risk. By employing summary statistics from the latest and most extensive genome-wide association studies (GWAS), we performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between PD and a variety of 17 AIDs, encompassing multiple sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, asthma, inflammatory bowel disease, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary biliary cirrhosis, primary sclerosing cholangitis, type 1 diabetes, ankylosing spondylitis, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and vitiligo. Inverse-variance weighted (IVW) was adopted as the main statistical approach to obtain the causal estimates of PD on different AIDs, supplemented by a series of complementary analyses (weighted median, MR Egger regression, and MR-PRESSO) for further strengthening the robustness of results. Our MR findings suggested that genetically predicted higher liability to PD was causally associated with a decreased risk of irritable bowel syndrome (OR = 0.98; 95% CI: 0.96-0.99; P = 0.032). On the contrary, IVW analysis showed a potential positive correlation between genetically determined PD and the incidence of type 1 diabetes (OR = 1.10; 95%CI: 1.02-1.19; P = 0.010). Subsequent MR tests ended up in similar results, confirming our findings were reliable. Additionally, in the reverse MR analyses, we did not identify any evidence to support the causal relationship of genetic predisposition to AIDs with PD susceptibility. In general, a bifunctional role that PD exerted on the risk of developing AIDs was detected in our studies, both protecting against irritable bowel syndrome occurrence and raising the incidence of type 1 diabetes. Future studies, including population-based observational studies and molecular experiments in vitro and in vivo, are warranted to validate the results of our MR analyses and refine the underlying pathological mechanisms involved in PD-AIDs associations.

Yang J ，Lin W ，Ma Y ，Song H ，Mu C ，Wu Q ，Han C ，Zhang J ，Liu X ... -  《Frontiers in Immunology》