Inflammatory arthritis and eye diseases: a Mendelian randomization study
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PROVIDER: S-EPMC10591326 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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| S-EPMC10848324 | biostudies-literature
Project description:Observational studies have indicated that there is an association between rheumatoid arthritis (RA) and an elevated risk of hypertension. However, a definitive causal relationship between the two conditions has not been established. The objective of this study was to investigate the causal link between RA and hypertension, as well as the potential mediating role of circulating inflammatory proteins in this relationship. We utilized Mendelian randomization (MR) to examine the causal relationship between RA and hypertension. The study data were obtained from publicly accessible genome-wide association study (GWAS) databases and meta-aggregates of large GWAS studies. The primary statistical method for determining causal effects was the inverse variance weighted (IVW) method, which was supplemented by a variety of sensitivity analyses. The results of the IVW method suggest a causal relationship between RA and an increased risk of hypertension (OR = 1.03, 95% CI = 1.01-1.04, p = 3.32 × 10-5). This association remained statistically significant even after adjusting for multiple confounding factors. Furthermore, MR analyses also revealed causal links between 10 circulating inflammatory proteins and the risk of hypertension, with TNF-related activation-induced cytokine partially mediating RA-induced hypertension at a mediator ratio of 11.17% (0.27%-22.08%). Our study identifies causal relationships between several genetically determined inflammatory proteins and hypertension, establishing that RA increases hypertension risk, with inflammation partially mediating this effect. These findings provide new evidence supporting the inflammatory hypothesis in the mechanism of hypertension. Inflammatory factors may serve as potential targets for antihypertensive therapy.
| S-EPMC11771807 | biostudies-literature
Project description:The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown. In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR). We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran's Q tests. FDR correction was used to correct the p-values. IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane's Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results. Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.
| S-EPMC11289845 | biostudies-literature
Project description:Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study. Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran's Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction. Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66-0.89, and p = 3.66 × 10-4), SS (OR: 0.75, CI: 0.58-0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68-0.88, and p = 9.85 × 10-5), hypothyroidism (OR: 0.84, 95% CI: 0.78-0.91, and p = 7,08 × 10-6), hyperthyroidism (OR: 0.60, 95% CI: 0.44-0.83, and p = 1.90 × 10-3), sarcoidosis (OR: 0.67, 95% CI: 0.54-0.83, and p = 2.60 × 10-4), and IPF (OR: 0.41, 95% CI: 0.29-0.58, and p = 4.11 × 10-7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18-1.94, and p = 9.66 × 10-4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62-1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37-2.54, and p = 8.01 × 10-5). Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.
| S-EPMC10150136 | biostudies-literature
Project description:Several studies have examined environmental factors and inflammatory bowel diseases (IBD) using traditional approaches; however, provided results are still conflicting. Our aim was to determine whether lifestyle and nutrient exposures, related to IBD in observational meta-analyses, influence IBD risk using a Mendelian randomization (MR) approach. A two-sample MR approach was applied on summary-level genome-wide association results. Genetic variants strongly associated with measures of tobacco smoking, obesity and fat distribution, physical activity, and blood levels of vitamins and fatty acids were evaluated on genetic data from international IBD consortia including a total of 25,042 IBD cases (12,194 cases of Crohn's disease (CD) and 12,366 cases of ulcerative colitis (UC)) and 34,915 controls. Our results indicated that, among lifestyle exposures, being a smoker was positively associated with CD (OR 1.13, P = 0.02), but it was not associated with UC risk (OR 0.99, P = 0.88). Body-mass index (BMI) and body fat percentage were positively associated with CD (OR 1.11, P = 0.02, per standard deviation (SD) of 4.6 kg/m2; and OR 1.50, P = 3 × 10-10, per SD of 6.6%; respectively); while for UC, BMI was inversely associated (OR 0.85, P = 5 × 10-5; per SD) and body fat percentage showed a OR of 1.11 (P = 0.11; per SD). Additionally, among nutrient exposures, omega-3 fatty acids levels were inversely associated with CD (OR 0.67, P = 2 × 10-6). Our MR results did not support a protective effect for being a smoker on UC risk; however, they are compatible with a risk effect for higher body fat proportion and a protective role for higher levels of omega-3 fatty acids on CD etiology.
| S-EPMC7648100 | biostudies-literature
Project description:BackgroundObservational studies have shown an increased risk of ocular inflammatory diseases in patients with ankylosing spondylitis (AS), but the genetically predicted association remains unclear. The aim of this study was to systematically assess the causal relationship between AS and ocular inflammatory diseases.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between AS and several common ocular inflammatory diseases based on genome-wide association study (GWAS) data and public health data. Five methods, namely, inverse-variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode, were used. Sensitivity analysis was performed using MR-Egger intercept, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), Cochran's Q test, outlier methods, leave-one-out analysis, and funnel plots.ResultsThe MR analysis showed a significantly increased risk of uveitis (ORIVW = 2.825, 95%CIIVW = 1.709-4.672, and PIVW < 0.001), iridocyclitis (ORIVW = 3.806, 95%CIIVW = 2.809-5.157, and PIVW < 0.001), scleritis (ORIVW = 1.738, 95%CIIVW = 1.190-2.539, and PIVW < 0.001), and episcleritis (ORIVW = 5.113, 95%CIIVW = 2.067-12.645, and PIVW = 0.004) associated with AS. However, no correlation was found between genetically predicted AS and keratitis (ORIVW = 1.041, 95%CIIVW = 0.886-1.222, and PIVW = 0.628) and optic neuritis (ORIVW = 0.868, 95%CIIVW = 0.441-1.709, and PIVW = 0.682).ConclusionAS increases the genetically predicted risk for uveitis, iridocyclitis, scleritis, and episcleritis. No potential association of AS with keratitis and optic neuritis was found. It may provide clues for the prevention of AS complications.
| S-EPMC11524906 | biostudies-literature
Project description:IntroductionImmune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE.MethodsWe collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness.ResultsIVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy.ConclusionThis MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.
| S-EPMC9792973 | biostudies-literature
Project description:BackgroundThere is increasing evidence pointing to a close relationship between sarcopenia and inflammatory bowel disease. However, it remains unclear whether or in which direction causal relationships exist, because these associations could be confounded.MethodsWe conducted a two-sample bidirectional mendelian randomization analysis using data from European genome-wide association studies of the appendicular lean mass(n = 450,243), walking pace(n = 459,915), grip strength (left hand, n = 461,026; right hand, n = 461,089), inflammatory bowel disease (25,042 patients and 34,915 controls), ulcerative colitis (12,366 patients and 33,609 controls), and Crohn's disease (12,194 patients and 28,072 controls) to investigate the causal relationship between sarcopenia-related traits and inflammatory bowel disease and its subtypes on each other. The inverse-variance weighted method was used as the primary analysis method to assess the causality, and a comprehensive sensitivity test was conducted.ResultsGenetically predicted appendicular lean mass was significantly associated with inflammatory bowel disease (OR = 0.916, 95%CI: 0.853-0.984, P = 0.017), ulcerative colitis (OR =0.888, 95%CI: 0.813-0.971, P = 0.009), and Crohn's disease (OR = 0.905, 95%CI: 0.820-0.999, P = 0.049). Similar results also revealed that the usual walking pace was causally associated with Crohn's disease (OR = 0.467, 95%CI: 0.239-0.914, P = 0.026). Reverse mendelian randomization analysis results found that genetic susceptibility to inflammatory bowel disease, and Crohn's disease were associated with lower appendicular lean mass. A series of sensitivity analyses ensured the reliability of the present research results.ConclusionThe mendelian randomization study supports a bidirectional causality between inflammatory bowel disease, Crohn's disease and appendicular lean mass, but no such bidirectional causal relationship was found in ulcerative colitis. In addition, genetically predicted usual walking pace may reduce the risk of Crohn's disease. These findings have clinical implications for sarcopenia and inflammatory bowel disease management.
| S-EPMC10666781 | biostudies-literature
Project description:Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), have become a global health problem with a rapid growth of incidence in newly industrialized countries. Observational studies have recognized associations between blood lipid traits and IBDs, but the causality still remains unclear. To determine the causal effects of blood lipid traits, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) on IBDs, two-sample Mendelian randomization (MR) analyses were conducted using the summary-level genome-wide association study (GWAS) statistics of blood lipid traits and IBDs. Our univariable MR using multiplicative random-effect inverse-variance weight (IVW) method identified TC (OR: 0.674; 95% CI: 0.554, 0.820; p < 0.00625) and LDL-C (OR: 0.685; 95% CI: 0.546, 0.858; p < 0.00625) as protective factors of UC. The result of our multivariable MR analysis further provided suggestive evidence of the protective effect of TC on UC risk (OR: 0.147; 95% CI: 0.025, 0.883; p < 0.05). Finally, our MR-BMA analysis prioritized TG (MIP: 0.336; θ^MACE: -0.025; PP: 0.31; θ^λ: -0.072) and HDL-C (MIP: 0.254; θ^MACE: -0.011; PP: 0.232; θ^λ: -0.04) for CD and TC (MIP: 0.721; θ^MACE: -0.257; PP: 0.648; θ^λ: -0.356) and LDL-C (MIP: 0.31; θ^MACE: -0.095; PP: 0.256; θ^λ: -0.344) for UC as the top-ranked protective factors. In conclusion, the causal effect of TC for UC prevention was robust across all of our MR approaches, which provide the first evidence that genetically determined TC is causally associated with reduced risk of UC. The finding of this study provides important insights into the metabolic regulation of IBDs and potential metabolites targeting strategies for IBDs intervention.
| S-EPMC10300867 | biostudies-literature
Project description:ObjectivesTo investigate the causal relationships between pneumoconiosis and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and gout.MethodsThe random-effects inverse variance weighted (IVW) approach was utilized to explore the causal effects of the instrumental variables (IVs). Sensitivity analyses using the MR-Egger and weighted median (WM) methods were did to investigate horizontal pleiotropy. A leave-one-out analysis was used to avoid the bias resulting from single-nucleotide polymorphisms (SNPs).ResultsThere was no causal association between pneumoconiosis and SLE, RA or gout in the European population [OR = 1.01, 95% CI: 0.94-1.10, p = 0.74; OR = 1.00, 95% CI: 0.999-1.000, p = 0.50; OR = 1.00, 95% CI: 1.000-1.001, p = 0.55]. Causal relationships were also not found in pneumoconiosis due to asbestos and other mineral fibers and SLE, RA and gout [OR = 1.01, 95% CI: 0.96-1.07, p = 0.66; OR = 1.00, 95% CI: 1.00-1.00, p = 0.68; OR = 1.00, 95% CI: 1.00-1.00, p = 0.20].ConclusionOur study suggests that pneumoconiosis may have no causal relationship with the three inflammatory immune diseases.
| S-EPMC11004292 | biostudies-literature