Causal association between common rheumatic diseases and glaucoma: a Mendelian randomization study
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ABSTRACT:
SUBMITTER: Meng Y
PROVIDER: S-EPMC10550209 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundObservational studies have suggested a link between rheumatic diseases and arrhythmias. However, these studies have been limited by confounding factors and reverse causality, leaving the causal relationship between rheumatic diseases and arrhythmias uncertain. This study addresses this inquiry using genetic evidence.MethodsSelected single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) data were employed as instrumental variables. Inverse variance weighting (IVW), MR-Egger regression, and the weighted median method were utilized in the two-sample Mendelian randomization analysis. Horizontal pleiotropy was identified and rectified through the MR-PRESSO test and MR-Egger regression. The stability and reliability of the Mendelian randomization results were appraised using the remain-one method, Cochran Q-test, and funnel plot. Odds ratios (OR) were utilized to assess the causal relationship between six rheumatic diseases and five types of arrhythmias.ResultsThe Inverse Variance Weighted (IVW) method indicated a significant association between rheumatoid arthritis (RA) and an elevated risk of right bundle branch block (RBBB) (OR: 1.10, 95% CI: 1.02-1.18, p = 0.009). Additionally, gout was significantly correlated with an augmented risk of RBBB (OR: 1.28, 95% CI: 1.09-1.51, p = 0.003). Conversely, dermatomyositis (DM) exhibited a negative association with the risk of atrioventricular block (AVB) (OR: 0.94, 95% CI: 0.90-0.99, p = 0.020). No significant associations were observed between other rheumatic diseases and arrhythmias.ConclusionA two-sample Mendelian Randomization (MR) study provides data indicating that in European populations, a genetically predicted gout or rheumatoid arthritis (RA) may increase the incidence of right bundle branch block (RBBB). To clarify and investigate the processes behind these causal links, more research is necessary. Because racial genetic variability exists, care should be used when interpreting our findings.
| S-EPMC11473426 | biostudies-literature
Project description:Cardiovascular diseases and dermatological conditions are prevalent health issues worldwide. Previous studies have suggested that risk factors for cardiovascular diseases may be associated with the development of dermatological conditions. However, the causal association between these factors remain unclear. This study utilized data from genome-wide association studies and applied Mendelian randomization (MR) to explore the potential causal association between cardiovascular risk factors and common dermatological conditions. Genetic variants significantly associated with low-density lipoprotein cholesterol (LDL-C), serum uric acid, blood glucose, and hypertension were selected as instrumental variables. We employed inverse variance weighted, MR Egger, and weighted mode methods for analysis. Sensitivity analyses, including Cochran Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis, were conducted to ensure the robustness of the results. The MR analysis indicated a positive association between LDL-C levels and the risk of psoriasis (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.03-1.47, P = .02). Additionally, hypertension and serum uric acid levels were positively associated with the risk of dermatitis eczema (hypertension: OR = 2.77, 95% CI: 1.23-6.24, P = .01; serum uric acid: OR = 1.09, 95% CI: 1.01-1.06, P = .01). This study provides evidence of a potential causal association between LDL-C levels and psoriasis, as well as between hypertension and serum uric acid levels and dermatitis eczema. These findings highlight the potential importance of cardiovascular health management in the prevention and treatment of common dermatological conditions. Further research is needed to validate these results and explore the underlying biological mechanisms.
| S-EPMC11630946 | biostudies-literature
Project description:BackgroundGlobally, oral diseases are common, pose an economic burden, and significantly decline the quality of life of affected individuals. Recently, researchers have substantially highlighted the effect of depression on oral disease incidence and development. In this study, we elucidated the correlation between depression and oral diseases.MethodsUsing two-sample Mendelian randomization (MR), the association between depression and the risk of 17 oral diseases was evaluated. Three methods were used to perform MR analysis: the inverse variance-weighted, weighted median, and MR-Egger methods. Furthermore, Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, and leave-one-out analysis were performed to analyze sensitivity.ResultsAfter implementing multiple test corrections, we observed that genetic susceptibility to depression was associated with an increased risk of mouth ulcers, toothache, loose teeth, bleeding gums, painful gums, chronic periodontitis, chronic tonsil and adenoid diseases, peritonsillar abscess, and excessive tooth attrition. However, a causal relationship between depression and other oral diseases was not observed. Sensitivity analysis confirmed the robustness of the results.ConclusionsWe confirmed the causal relationship between depression and several oral diseases, thereby providing a novel viewpoint on the prevention and treatment of oral diseases. Our findings suggest the integration of depression control into routine clinical care to enhance the effectiveness of oral disease treatment.
| S-EPMC10742945 | biostudies-literature
Project description:BackgroundCardiovascular diseases (CVD), including coronary heart disease (CHD), heart failure, ischemic heart disease (IHD), and atrial fibrillation, are prevalent in the aged. However, the influence of CVD on ED is less investigated. This study was performed to clarify the causal association between CVD and ED.Materials and methodsGenome-wide association studies (GWAS) datasets targeting CHD, heart failure, IHD, and atrial fibrillation were downloaded to retrieve single nucleotide polymorphisms (SNPs). Further, single-variable Mendelian randomization and multivariable Mendelian randomization (MVMR) were adopted to explore the causal association between CVD and ED.ResultsGenetically predicted CHD and heart failure were found to increase the risks of ED (OR = 1.09, P < 0.05 and OR = 1.36, P < 0.05, respectively). However, no causal association was disclosed among IHD, atrial fibrillation and ED (all P > 0.05). These findings remained consistent in sensitivity analyses. After controlling for body mass index, alcohol, low density lipoprotein, smoking and total cholesterol levels, the results of MVMR support the causal role of CHD on ED (P < 0.05). Similarly, the direct causal effect estimates of heart failure on ED were significant in MVMR analyses (P < 0.05).ConclusionUsing genetic data, this study revealed that genetically predicted CHD and heart failure may predict better ED compared with atrial fibrillation and IHD. The results should be interpreted with caution and the insignificant causal inference of IHD still needs further verification in future studies.
| S-EPMC9947236 | biostudies-literature
Project description: Not available
| S-EPMC11328884 | biostudies-literature
Project description:BackgroundAge-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes.MethodsInstrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates.ResultsThe results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E-04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (β = -0.190 year, 95% CI -0.374 to -0.008, P = 0.041). The EEA of HannumAge (β = -0.85 μm, 95% CI -1.57 to -0.14, P = 0.019) and HorvathAge (β = -0.63 μm, 95% CI -1.18 to -0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (β = 0.06 μm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05).ConclusionThe present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.
| S-EPMC11325616 | biostudies-literature
Project description:Air pollution is strongly associated with autoimmune diseases (ADs), however, the genetic causality between them remains poorly understood. Therefore, the aim of this study is to determine the relationship between common air pollutants and ADs through Mendelian randomization (MR) analysis. We conducted a MR study using aggregated data from publicly available genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) associated with 5 common air pollutants are used as instrumental variables. Random-effects inverse variance weighted (IVW) is used as the primary method to assess causal relationships, with results reported in terms of odds ratios (OR). In addition, we used a two-step MR to assess the mediating role of common risk factors for ADs in the effects of air pollution on ADs. Our analysis revealed causal associations between selected air pollutants and specific ADs. Exposure to nitrogen oxides was positively associated with the risk of rheumatoid arthritis (RA) (OR = 1.47,95% CI 1.01-2.14, P = 0.043), Sjogren's syndrome (SS) (OR = 2.29,95% CI 1.08-4.89, P = 0.032), and systemic lupus erythematosus (OR = 7.26,95% CI 2.25-23.40, P = 9.10E-04). Genetically predicted PM2.5 and PM10 were risk factors for ulcerative colitis (OR = 1.68,95% CI 1.05-2.68, P = 0.032) and psoriasis (OR = 1.34,95% CI 1.02-1.76, P = 0.037), respectively. Our results also suggest a negative causal relationship between PM2.5-10 and SS (OR = 0.29, 95% CI 0.10-0.90, P = 0.032). In risk factor-related mediation analyses, BMI and smoking mediated 6% (95% CI 1-10%) and 9% (95% CI 2-17%) of the effect of nitrogen oxides on RA, respectively. This study provides evidence of a causal relationship between air pollutants and specific ADs risks, suggesting that improving air pollution may be important in preventing ADs.
| S-EPMC11697238 | biostudies-literature
Project description:BackgroundAn association has been observed between primary biliary cholangitis (PBC) and systemic rheumatic diseases (SRDs) in observational studies, however the exact causal link remains unclear. We aimed to evaluate the causal effects of PBC on SRDs through Mendelian randomization (MR) analysis.MethodsThe genome-wide association study (GWAS) summary data were obtained from MRC IEU OpenGWAS and FinnGen databases. Independent genetic variants for PBC were selected as instrumental variables. Inverse variance weighted was used as the main approach to evaluate the causal effects of PBC on Sjögren syndrome (SS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD) and polymyositis (PM). Horizontal pleiotropy and heterogeneity were measured by MR‒Egger intercept test and Cochran's Q value, respectively.ResultsPBC had causal effects on SS (OR = 1.177, P = 8.02e-09), RA (OR = 1.071, P = 9.80e-04), SLE (OR = 1.447, P = 1.04e-09), SSc (OR = 1.399, P = 2.52e-04), MCTD (OR = 1.306, P = 4.92e-14), and PM (OR = 1.416, P = 1.16e-04). Based on the MR‒Egger intercept tests, horizontal pleiotropy was absent (all P values > 0.05). The robustness of our results was further enhanced by the leave-one-out method.ConclusionsOur research has provided new insights into PBC and SRDs, indicating casual effects on various SRDs.
| S-EPMC11360496 | biostudies-literature
Project description:PurposeThis Mendelian randomization (MR) analysis study aimed to investigate the genetic causal relationship between non-thyroidal autoimmune diseases (ADs) and Graves' ophthalmopathy (GO).MaterialsSingle nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis vulgaris (PV), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) were obtained from the IEU Open genome-wide association studies (GWAS) database, GWAS data for GO were obtained from the FinnGen database. Bidirectional MR analysis was conducted using inverse variance weighted (IVW) method, weighted median (WM) method and MR-Egger test. Cochran's Q statistic was used to assess the heterogeneity between SNP estimates. MR-Egger regression was used to evaluate horizontal pleiotropy and MR pleiotropy residual sum and outlier (MR-PRESSO) test was used to detect the outliers.ResultsFor non-thyroidal ADs, the forward MR results using the IVM method showed that T1D (OR = 1.259, 95%CI 1.026-1.5465; P = 0.028) and SLE (OR = 1.807, 95%CI 1.229-2.655; P = 0.003) were correlated with the risk of GO at the genetic level, while there was no evidence showing that IBD, MS, PV and RA were correlated with GO. In the reverse MR study, there was a significant increase in the risk of developing T1D in GO (OR = 1.135, 95%CI 1.018-1.265; P = 0.022), but pleiotropy and heterogeneity existed.ConclusionsIn the European population, there is strong genetic evidence that patients with T1D and SLE have a higher risk of developing GO, whereas the effect of GO on ADs is unclear.
| S-EPMC11869498 | 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