Dataset Information

Effects of heart failure and coronary artery disease on erectile dysfunction: a two-sample mendelian randomization study.

ABSTRACT:

Background and aims

There are no clear conclusions as to whether heart failure (HF) and coronary heart disease (CAD) increase the risk of erectile dysfunction (ED).In our study, we used Mendelian randomization (MR) analysis to discover a causal relationship between HF, CAD and ED.

Methods

Single nucleotide polymorphisms (SNPs) associated with HF, CAD and ED were obtained from the MRC IEU Open Genome-Wide Association Study (GWAS) database.After a series of screenings, the remaining SNPs were selected as instrumental variables (IVs) for HF and CAD for MR analysis to assess the relationship between genetically predicted HF or CAD and the pathogenesis of ED.Among them, we used the random-effects inverse variance weighted (IVW) method as the primary analysis method.Finally, Cochran's q-test, funnel plots, MR-Egger regression, Leave-one-out method and MR-PRESSO were used for sensitivity analysis.

Results

In the IVW method, there was no significant causal relationship between genetically predicted HF and CAD and the incidence of ED.(HF: OR = 1.17, 95% CI 0.99-1.39; p = 0.074;CAD: OR = 1.08, 95% CI 0.99-1.17, p = 0.068)。The results of sensitivity analyses supported our conclusion that no horizontal pleiotropism was found.

Conclusion

This study did not find a causal relationship between HF or CAD and ED in European populations, which requires further in-depth research.

SUBMITTER: Shao K

PROVIDER: S-EPMC10576338 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Effects of heart failure and coronary artery disease on erectile dysfunction: a two-sample mendelian randomization study.

Shao Kaiyang K Chen Weikang W Li Yaling Y Zheng Huiyan H Hu Ruying R Zhang Jianqiao J Sun Ting T

BMC urology 20231014 1

<h4>Background and aims</h4>There are no clear conclusions as to whether heart failure (HF) and coronary heart disease (CAD) increase the risk of erectile dysfunction (ED).In our study, we used Mendelian randomization (MR) analysis to discover a causal relationship between HF, CAD and ED.<h4>Methods</h4>Single nucleotide polymorphisms (SNPs) associated with HF, CAD and ED were obtained from the MRC IEU Open Genome-Wide Association Study (GWAS) database.After a series of screenings, the remaining ...[more]

PMID: 37833702

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Project description:BackgroundSeveral observational studies have reported the correlation between gut microbiota and the risk of erectile dysfunction (ED). However, the causal association between them remained unestablished owing to intrinsic limitations, confounding factors, and reverse causality. Therefore, the two-sample Mendelian randomization (MR) study was performed to determine the causal effect of gut microbiota on the risk of ED.MethodsThe MR analysis utilized the publicly available genome-wide association study (GWAS) summary-level data to explore the causal associations between gut microbiota and ED. The gut microbiota data were extracted from the MiBioGen study (N = 18,340), and the ED data were extracted from the IEU Open GWAS (6,175 ED cases and 217,630 controls). The single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) by two thresholds of P-values, the first P-value setting as <1e-05 (locus-wide significance level) and the second P-value setting as <5e-08 (genome-wide significance level). The inverse variance weighted approach was used as the primary approach for MR analysis, supplemented with the other methods. In addition, sensitivity analyses were performed to evaluate the robustness of the MR results, including Cochran's Q test for heterogeneity, the MR-Egger intercept test for horizontal pleiotropy, the Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) global test for outliers, and the forest test and leave-one-out test for strong influence SNPs.ResultsOur results presented that the increased abundance of Lachnospiraceae at family level (OR: 1.265, 95% CI: 1.054-1.519), Senegalimassilia (OR: 1.320, 95% CI: 1.064-1.638), Lachnospiraceae NC2004 group (OR: 1.197, 95% CI: 1.018-1.407), Tyzzerella3 (OR: 1.138, 95% CI: 1.017-1.273), and Oscillibacter (OR: 1.201, 95% CI: 1.035-1.393) at genus level may be risk factors for ED, while the increased abundance of Ruminococcaceae UCG013 (OR: 0.770, 95% CI: 0.615-0.965) at genus level may have a protective effect on ED. No heterogeneity or pleiotropy was found based on the previously described set of sensitivity analyses.ConclusionOur MR analysis demonstrated that the gut microbiota had inducing and protective effects on the risk of ED. The results provide clinicians with novel insights into the treatment and prevention of ED in the future. Furthermore, our study also displays novel insights into the pathogenesis of microbiota-mediated ED.

Project description:ObjectiveStudies have found that gut microbiota may be associated with the development of erectile dysfunction (ED); however, the exact link between the two remains unclear. This study aimed to elucidate the relationship between the gut microbiota and the risk of ED from a genetic perspective.MethodsWe investigated the relationship between the gut microflora and ED using two-sample Mendelian randomization. GWAS-pooled data for ED were obtained from 223805 participants in Europe. GWAS summary data for ED were obtained from 223805 subjects in Europe and that for the gut microbiota were obtained from 18340 participants in 24 cohorts. We used the inverse-variance weighted (IVW) estimator as the primary method for the preliminary analysis, and the MR-Egger, weighted median (WM), simple model, and weighted model as secondary methods. We used Cochrane's Q-test, to detect heterogeneity, MREgger to detect pleiotropy, and the leave-one-out method to test the stability of the MR results. Ultimately, we genetically predicted a causal relationship between 211 gut microbiota and ED.ResultsA total of 2818 SNPs associated with gut microflora were screened in the ED correlation analysis based on the assumption of instrumental variables. The results of MR analysis showed a causal relationship between the six gut microbes and ED occurrence. The results of the fixed effects IVW method revealed five gut microflora, including Lachnospiraceae (OR, 1.265; P = 0.008), Lachnospiraceae NC2004 group (OR, 1.188; P = 0.019), Oscillibacter (OR, 1.200; P = 0.015), Senegalimassilia (OR, 1.355; P = 0.002), Tyzzerella3 (OR, 1.133; P = 0.022), to be negatively associated with ED. In addition, the IVW method revealed Ruminococcaceae UCG-013 (OR, 0.827; P = 0.049) to be positively associated with ED. Quality control results showed no heterogeneity or horizontal pleiotropy in the MR analysis (P > 0.05).ConclusionsSix gut microbes were genetically associated with ED; of which, Ruminococcaceae UCG-013 was causally associated with a reduced risk of ED development. Our findings provide a new direction for research on the prevention and treatment of ED; however, the mechanisms and details require further investigation.

Project description:BackgroundPrevious studies have investigated the association between immune inflammation, metabolism and erectile dysfunction (ED). However, these studies are limited by biases, confounding factors, and reverse causality, failing to establish causality. We conducted a two-sample Mendelian randomization (MR) study to elucidate the causal relationships between immune cells, inflammatory cytokines, plasma metabolites, and the risk of ED.MethodsData on 91 inflammatory cytokines (n=14,736), 731 immune phenotypes (n=3,757) and 1,400 circulating metabolites (n=8,000) were obtained from genome-wide association studies (GWAS) as exposures, while ED data were sourced from the Integrative Epidemiology Unit (IEU) Open GWAS database (n=223,805) as outcomes. A two-sample MR analysis was performed to determine the relationships between exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary MR analysis approach, supplemented by additional methods. Sensitivity analyses, including Cochran's Q test for heterogeneity and MR-Egger intercept for horizontal pleiotropy, were conducted to assess the robustness of the MR results.ResultsAt a significance level of P<0.01, we identified 12 factors associated with ED: five immune cells, one inflammatory cytokine, two metabolites, and four metabolite ratios. Specifically, CD19 on immunoglobulin D- (IgD-) CD38+ B cells [odds ratio (OR) =1.17; 95% confidence interval (CI): 1.06-1.30], CD4 on terminally differentiated CD4+ T cells (OR =1.07; 95% CI: 1.02-1.12), CD25 on IgD+ CD38dim B cells (OR =1.05; 95% CI: 1.01-1.09), CD25 on IgD+ CD24- B cells (OR =1.04; 95% CI: 1.01-1.07), and IgD on IgD+ B cells (OR =0.88; 95% CI: 0.79-0.97) were associated with ED. Among inflammatory cytokines, only elevated levels of urokinase-type plasminogen activator (uPA) significantly reduced the risk of ED (OR =0.83; 95% CI: 0.73-0.95). Six metabolites, including glycerol levels (OR =1.30; 95% CI: 1.08-1.56), aspartate to N-acetylglucosamine to N-acetylgalactosamine ratio (OR =1.21; 95% CI: 1.07-1.37), cholesterol to taurocholate ratio (OR =1.23; 95% CI: 1.07-1.42), 4-methyl-2-oxopentanoate to 3-methyl-2-oxobutyrate ratio (OR =1.26; 95% CI: 1.07-1.48), alpha-ketoglutarate to kynurenine ratio (OR =0.86; 95% CI: 0.76-0.96), and X-16964 levels (OR =1.24; 95% CI: 1.06-1.45) were significantly associated with ED. Sensitivity analyses did not reveal any heterogeneity or pleiotropy.ConclusionsOur MR analysis indicates that immune inflammation and metabolism have both inducing and protective effects on ED risk. These findings provide new insights for clinicians regarding the treatment and prevention of ED. Additionally, our study offers novel insights into the pathogenesis of ED.

Project description:BackgroundRecently, some observational studies have suggested potential associations between erectile dysfunction (ED) and respiratory function. However, the underlying biological mechanisms and causal relationships between ED and lung function require further investigation. This study aimed to explore the causalities between ED and lung function traits.MethodsSingle-nucleotide polymorphisms (SNPs) for ED were extracted from the Finngen_r7 (1,154 cases and 94,024 controls), and the summary statistics of respiratory function were extracted from the UK Biobank (UKB) (n=321,047). We utilized several Mendelian randomization (MR) methods to mitigate the impact of weak instrument bias and pleiotropy. To address potential confounding effects, multivariable MR (MVMR) analyses were also conducted, adjusting for demographic factors and respiratory conditions. Moreover, recently developed latent causal variable (LCV) modeling was also performed to enhance the robustness of the findings.ResultsTotally 15 SNPs robustly associated with ED were included. We found that higher risk of ED was associated with decreased of forced expiratory volume in the first second (FEV1) [odds ratio (OR) 0.992, 95% confidence interval (CI): 0.986, 0.997, P=0.003], as was the case for forced vital capacity (FVC) (OR 0.994, 95% CI: 0.989, 1.000, P=0.04), peak expiratory flow (PEF) (OR 0.990, 95% CI: 0.990, 0.990, P=0.01) and FEV1/FVC ratio (OR 0.991, 95% CI: 0.985, 0.997, P=0.002). After adjusting for confounding factors, ED only demonstrated causal effects on FEV1/FVC ratio. Notably, the LCV analysis provided additional support for the positive causal impact of ED on FEV1 and FVC. Conversely, reverse MR analysis did not reveal compelling evidence for a causal effect of lung function on ED.ConclusionsOur study suggests a potential causal relationship between higher ED susceptibility and reduced respiratory function, as indicated by decreased FEV1, FVC, PEF, and the FEV1/FVC ratio. The results enhanced understanding of the intricate interrelationships between ED and lung function.

Dataset Information

Effects of heart failure and coronary artery disease on erectile dysfunction: a two-sample mendelian randomization study.

Background and aims

Methods

Results

Conclusion

Publications

Effects of heart failure and coronary artery disease on erectile dysfunction: a two-sample mendelian randomization study.

Similar Datasets

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