Multigenomics Reveals the Causal Effect of Herpes Simplex Virus in Alzheimer's Disease: A Two-Sample Mendelian Randomization Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang Y
PROVIDER: S-EPMC8766664 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundObservational studies have indicated the association of alteration of adipokines with Alzheimer's disease (AD). However, it remains unclear whether the associations are causal.ObjectiveTo determine the causal associations between adipokines and AD.MethodsA Mendelian randomization (MR) method was applied to investigate the causal relationships of adipokines, including adiponectin and resistin, with risk of AD. Genetic proxies from genome-wide association studies (GWAS) of adiponectin and resistin were selected as instrumental variables. GWAS summary statistics for AD were extracted as outcome.ResultsIn this study, we found evidence of the causal effects of adiponectin on AD (OR: 0.850, 95% CI: 0.731-0.990, p = 0.037). However, no relationship between resistin and AD (OR: 0.936, 95% CI: 0.851-1.029, p = 0.171) was detected. In the reverse causation analysis, null associations of AD were found for adiponectin and resistin (all p > 0.05).ConclusionsThis study provides evidence of causality between adiponectin and risk of AD. However, no genetic susceptibility of resistin was discovered for AD.
| S-EPMC10836602 | biostudies-literature
Project description:BackgroundPrevious observational studies have reported that delirium has an association with an increased risk of Alzheimer's disease (AD), and that patients with AD have a higher risk of developing delirium. However, due to the limitations of observational study, it is challenging to confirm whether delirium has a causal effect on AD or reverse causation exists.MethodsA bidirectional two-sample Mendelian randomization (MR) was performed to investigate the relationship between delirium and AD. Summary statistics from genome-wide association studies of delirium and AD phenotypes were utilized. Inverse-variance weighted (IVW) method was used as the main analysis approach, and additional analyses were performed using MR Egger, weighted median, simple mode and weighted mode to ensure result accuracy. Heterogeneity and horizontal pleiotropy were assessed using Cochran's Q statistics and MR Egger intercept, separately.ResultsThe MR analyses showed that genetically predicted delirium was not associated with AD (IVW: odds ratio [OR] 0.98, 95% CI 0.91-1.05, P = 0.544; MR Egger: OR 0.98, 95% CI 0.83-1.15, P = 0.780; weighted median: OR 0.96, 95% CI 0.88-1.05, P = 0.323; simple mode: OR 0.91, 95% CI 0.80-1.04, P = 0.212; weighted mode: OR 0.93, 95% CI 0.83-1.05, P = 0.277). However, in the reverse direction, AD was associated with delirium (IVW: OR 1.32, 95% CI 1.13-1.54, P = 3.91E-04; MR Egger: OR 1.42, 95% CI 1.02-1.98, P = 5.60E-02; Weighted median: OR 1.39, 95% CI 1.18-1.63, P = 8.22E-05; Simple mode: OR 1.41, 95% CI 1.10-1.80, P = 1.41E-02; Weighted mode: OR 1.39, 95% CI 1.16-1.67, P = 3.23E-03).ConclusionBased on the results of our MR study, there is no bidirectional causality between delirium and AD, delirium is not associated with an increased risk of AD, while genetically predicted AD is a potential causal risk factor for delirium.
| S-EPMC10405368 | biostudies-literature
Project description:BackgroundThis study aims to explore the relationship between psychiatric disorders and the risk of epilepsy using Mendelian randomization (MR) analysis.MethodsWe collected summary statistics of seven psychiatric traits from recent largest genome-wide association study (GWAS), including major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and insomnia. Then, MR analysis estimates were performed based on International League Against Epilepsy (ILAE) consortium data (ncase = 15,212 and ncontrol = 29,677), the results of which were subsequently validated in FinnGen consortium (ncase = 6260 and ncontrol = 176,107). Finally, a meta-analysis was conducted based on the ILAE and FinnGen data.ResultsWe found significant causal effects of MDD and ADHD on epilepsy in the meta-analysis of the ILAE and FinnGen, with corresponding odds ratios (OR) of 1.20 (95% CI 1.08-1.34, p = .001) and 1.08 (95% CI 1.01-1.16, p = .020) by the inverse-variance weighted (IVW) method respectively. MDD increases the risk of focal epilepsy while ADHD has a risk effect on generalized epilepsy. No reliable evidence regarding causal effects of other psychiatric traits on epilepsy was identified.ConclusionsThis study suggests that major depressive disorder and attention deficit hyperactivity disorder may causally increase the risk of epilepsy.
| S-EPMC10097067 | biostudies-literature
Project description:Background: Traditional observational studies have demonstrated an association between heart failure and Alzheimer's disease. The strengths of observational studies lie in their speed of implementation, cost, and applicability to rare diseases. However, observational studies have several limitations, such as uncontrollable confounders. Therefore, we employed Mendelian randomization of genetic variants to evaluate the causal relationships existing between AD and HF, which can avoid these limitations. Materials and Methods: A two-sample bidirectional MR analysis was employed. All datasets were results from the UK's Medical Research Council Integrative Epidemiology Unit genome-wide association study database, and we conducted a series of control steps to select the most suitable single-nucleotide polymorphisms for MR analysis, for which five primary methods are offered. We reversed the functions of exposure and outcomes to explore the causal direction of HF and AD. Sensitivity analysis was used to conduct several tests to avoid heterogeneity and pleiotropic bias in the MR results. Results: Our MR studies did not support a meaningful causal relationship between AD on HF (MR-Egger, p = 0.634 > 0.05; weighted median (WM), p = 0.337 > 0.05; inverse variance weighted (IVW), p = 0.471 > 0.05; simple mode, p = 0.454 > 0.05; weighted mode, p = 0.401 > 0.05). At the same time, we did not find a significant causal relationship between HF and AD with four of the methods (MR-Egger, p = 0.195 > 0.05; IVW, p = 0.0879 > 0.05; simple mode, p = 0.170 > 0.05; weighted mode, p = 0.110 > 0.05), but the WM method indicated a significant effect of HF on AD (p = 0.025 < 0.05). Because the statistical powers of IVW and MR-Egger are more than that of WM, we think that there is no causal effect of HF on AD. Sensitivity analysis and horizontal pleiotropy were not detected in the MR analysis. Conclusion: Our results did not provide significant evidence indicating any causal relationships between HF and AD in the European population. Therefore, more large-scale datasets or datasets related to similar factors are expected for further MR analysis.
| S-EPMC8787319 | biostudies-literature
Project description:Background: Colorectal cancer and Alzheimer's disease are both common life-threatening diseases in the elderly population. Some studies suggest a possible inverse relationship between colorectal cancer and Alzheimer's disease, but real-world research is subject to many biases. We hope to clarify the causal relationship between the two through a bidirectional two-sample Mendelian randomization study. Methods: In our study, we used genetic summary data from large-scale genome-wide association studies to investigate the relationship between colorectal cancer and Alzheimer's disease. Our primary analysis employed the inverse-variance weighted method and we also used complementary techniques, including MR-Egger, weighted median estimator, and Maximum likelihood. We applied simex adjustment to the MR-Egger results. We also utilized the MRlap package to detect potential sample overlap and its impact on the bias of the results. In addition, we performed several sensitivity and heterogeneity analyses, to ensure the reliability of our results. Results: The combined effect size results of the inverse-variance weighted method indicate that colorectal cancer may decrease the incidence of Alzheimer's disease, with an odds ratio (OR) of 0.846 (95% CI: 0.762-0.929). Similar results were observed using other methods such as MR-Egger, weighted median estimator, and Maximum likelihood. On the other hand, Alzheimer's disease may slightly increase the incidence of colorectal cancer, with an OR of 1.014 (95% CI: 1.001-1.027). However, the results of one subgroup were not significant, and the results from MRlap indicated that sample overlap introduced bias into the results. Therefore, the results of the reverse validation are not reliable. The F-statistic for all SNPs was greater than 20. Four SNPs related to the outcome were excluded using Phenoscanner website but the adjustment did not affect the overall direction of the results. The results of these statistics were further validated by MR-PRESSO, funnel plots, leave-one-out analyses, Cochran's Q, demonstrating the reliability of the findings. Conclusion: According to the findings of this Mendelian randomization study, there appears to be a causal association between colorectal cancer and Alzheimer's disease. These results could have important implications for clinical practice in terms of how colorectal cancer and Alzheimer's disease are treated. To better understand the relationship between these two diseases, more research and screening are needed in clinical settings.
| S-EPMC10797121 | biostudies-literature
Project description:Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10-8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.
| S-EPMC8791872 | biostudies-literature
Project description:IntroductionObjective observational studies have shown that basal metabolic rate (BMR) decreases in patients with Alzheimer's disease (AD), but the causal relationship between BMR and AD has not been established. We determined the causal relationship between BMR and AD by two-way Mendelian randomization (MR) and investigated the impact of factors associated with BMR on AD.MethodsWe obtained BMR (n = 454,874) and AD from a large genome-wide association study (GWAS) database (21,982 patients with AD, 41,944 controls). The causal relationship between AD and BMR was investigated using two-way MR. Additionally, we identified the causal relationship between AD and factors related with BMR, hyperthyroidism (hy/thy) and type 2 diabetes (T2D), height and weight.ResultsBMR had a causal relationship with AD [451 single nucleotide polymorphisms (SNPs), odds ratio (OR) 0.749, 95% confidence intervals (CIs) 0.663-0.858, P = 2.40E-03]. There was no causal relationship between hy/thy or T2D and AD (P > 0.05). The bidirectional MR showed that there was also a causal relationship between AD and BMR (OR 0.992, Cls 0.987-0.997, NSNPs18, P = 1.50E-03). BMR, height and weight have a protective effect on AD. Based on MVMR analysis, we found that genetically determined height and weight may be adjusted by BMR to have a causal effect on AD, not height and weight themselves.ConclusionOur study showed that higher BMR reduced the risk of AD, and patients with AD had a lower BMR. Because of a positive correlation with BMR, height and weight may have a protective effect on AD. The two metabolism-related diseases, hy/thy and T2D, had no causal relationship with AD.
| S-EPMC10195958 | biostudies-literature
Project description:BackgroundThere is now increasing evidence that type 2 diabetes mellitus (T2DM) is associated with Alzheimer's disease (AD). However, it is unclear whether the two are causally related.ObjectiveTo reveal the causal association between T2DM and AD, we performed a bidirectional Mendelian randomization (MR) analysis.MethodsGenetic instrumental variables were systematically screened, and inverse-variance weighting, MR-Egger regression, weighted median, simple mode, and weighted mode were applied to assess the pathogenic associations between the two diseases, and sensitivity analyses were used to further validate the robustness of the results.ResultsThe results of forward MR analysis with T2DM as the exposure were [OR = 0.998, 95% CI (0.975∼1.021), p = 0.857], and the results of reverse MR analysis with AD as the exposure were [OR = 0.966, 95% CI (0.934∼0.999), p = 0.043]. The results showed no significant association between T2DM and AD at the gene level (p < 0.025). Sensitivity analyses were consistent with the results of the main analysis, confirming the robustness of the study.ConclusionsT2DM and AD may not be genetically causally associated.
| S-EPMC11305840 | biostudies-literature
Project description:To investigate the causal relationship between attention deficit and hyperactivity disorder (ADHD) and frozen shoulder using Mendelian randomization (MR). Data were pooled from large-scale genome wide association studies, and genetic loci that were independent of each other and associated with ADHD and frozen shoulder in people of European ancestry were selected as instrumental variables. Three MR analyses, inverse variance weighting, weighted median and MR-Egger, were used to investigate the causal relationship between ADHD and frozen shoulder. Heterogeneity and multiplicity tests were used, and sensitivity analyses were performed using the "leave-one-out" method to explore the robustness of the results. The inverse variance weighting results showed an OR (95 % CI) of 1.12 (1.00-1.25), P = .046, indicating a causal relationship between ADHD and frozen shoulder. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. The present study used a two-sample MR analysis, and by analyzing and exploring the genetic data, the study showed that ADHD is a risk factor for developing frozen shoulder, and patients with ADHD are more likely to suffer from frozen shoulder.
| S-EPMC10627672 | biostudies-literature
Project description:To investigate the causal relationship between obesity and meniscal injuries using Mendelian randomization (MR). Genetic loci independently associated with obesity and meniscal injuries in people of European origin were selected as instrumental variables using pooled data from genome-wide association studies. Three MR analyses, MR-Egger, weighted median and inverse variance weighting, were used to investigate the causal relationship between obesity and meniscal injuries. The results were tested for robustness by heterogeneity and multiplicity tests, and sensitivity analyses were performed using the "leave-one-out" method. The inverse variance weighting results showed an OR (95% CI) of 1.13 (1.04-1.22), P = .003, indicating a causal relationship between obesity and the occurrence of meniscal injuries. And no heterogeneity and multiplicity were found by the test and sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using 2-sample MR analysis, and the results showed that obesity is a risk factor for meniscal injuries.
| S-EPMC10695575 | biostudies-literature