Power calculation for the general two-sample Mendelian randomization analysis.
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ABSTRACT:
SUBMITTER: Deng L
PROVIDER: S-EPMC8766247 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAlthough several observational studies have suggested positive associations between constipation and cardiovascular disease (CVD), a solid causal association has not been demonstrated. Therefore, a two-sample Mendelian randomization (MR) study was performed to investigate the causal associations between constipation and CVD.MethodsIndependent genetic variants strongly associated with constipation were obtained from the FinnGen consortium. Summary-level data for CVD, including coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), stroke, and its subtypes, were collected from a few extensive genome-wide association studies (GWASs). The inverse-variance weighted methods, weighted median, and MR-Egger were used for the MR estimates. The Cochran's Q test, MR-Egger intercept tests, MR-PRESSO, MR Steiger test, leave-one-out analyses, and funnel plot were used in the sensitivity analysis.ResultsGenetically determined constipation was suggestively associated with AF risk (odds ratio (OR), 1.07; 95% confidence interval (CI), 1.01, 1.14; p = 0.016). Constipation and other CVD do not appear to be causally related. It was demonstrated that the results were robust through sensitivity analyses.ConclusionThis MR study demonstrated suggestive causal associations of constipation on AF, despite no associations achieving a significance value after multiple testing corrections. There was no evidence of an association between constipation and the risk of CAD, MI, HF, stroke, or stroke subtypes.
| S-EPMC9998987 | biostudies-literature
Project description:Endometriosis, a prevalent condition, has long been recognized as a chronic and debilitating ailment affecting an estimated 1790 million women worldwide. Observational studies have established a correlation between endometriosis and ovarian cancer. Thus, we endeavored to employ Two-Sample Mendelian Randomization, utilizing summary statistics from a Genome-Wide Association Study of endometriosis and epithelial ovarian cancer, with genetic markers serving as proxies for epithelial ovarian cancer. The analysis revealed a significant correlation between these entities, with an odds ratio (OR) of 1.23 (95% CI 1.11-1.36). Upon histotype-specific examination, robust evidence emerged for an association of endometriosis with the risk of endometrioid carcinoma (OR 1.49, 95% CI 1.24-1.81), clear cell carcinoma (OR 2.56, 95% CI 1.75-3.73), and low malignant potential tumors (OR 1.28, 95% CI 1.08-1.53). These findings provide a theoretical framework for prospective investigations aimed at enhancing the potential therapeutic efficacy of managing endometriosis in averting the onset and progression of ovarian cancer.
| S-EPMC10713650 | biostudies-literature
Project description:BackgroundThere is a global increase in the prevalence of osteoporosis and chronic obstructive pulmonary disease (COPD). Studies based on observation revealed a higher incidence of osteoporosis in patients with COPD. We looked into the genetic relationship between COPD and osteoporosis using the Mendelian randomization (MR) technique.MethodsThe inverse variance-weighted (IVW) method was the primary technique used in this MR investigation. The sensitivity was assessed using the simple median, weighted median, penalized weighted median, and MR Egger regression analysis.ResultsThe IVW model demonstrated that genetically determined COPD is causally associated with an elevated risk of osteoporosis (odds ratio [OR] fixed-effect, 1.010; 95% confidence interval [CI], 1.001-1.019, P=0.021; OR random-effect, 1.010; 95% CI, 1.001-1.020, P=0.039). It was also found that this correlation held valid for the simple and weighted median, Penalized weighted, MR-Egger, and MR Egger (bootstrap) approaches. No heterogeneity was found in the IVW or MR-Egger analysis results (Q=131.374, P=0.061 and Q=128.895, P=0.069, respectively). Furthermore, no pleiotropic influence via genetic variations was revealed by MR-Egger regression (intercept, -0.0002; P=0.160). No one single nucleotide polymorphism was found to have a substantial impact on the relationship between COPD and osteoporosis by the leave-one-out sensitivity analysis.ConclusionOur MR analysis demonstrated a substantial positive impact of COPD on the risk of osteoporosis.
| S-EPMC11363972 | biostudies-literature
Project description:BackgroundAlthough epidemiological studies have shown a positive relationship between inflammatory bowel disease (IBD) and risk of cardiovascular disease (CVD) outcomes, a solid causal relationship has not been established. Thus, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effect between IBD and CVD outcomes.MethodsWe performed a two-sample MR analysis to analyze the causal effect of the IBD on CVD outcome by using summary-level genome-wide association studies of European descent. The inverse-variance weighted (IVW) method was used as the main MR analysis, with complementary analyses of MR Egger, maximum likelihood, weighted median, penalized weighted media, simple mode, weighted mode, and MR-PRESSO methods. Multiple sensitivity analyses were used to evaluate the robustness of our results.ResultsAll P-values were greater than 0.05 in the IVW method, showing no evidence of a causal association between circulating IBD and CVD. Similar results were observed by using other MR methods. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms was detected. Sensitivity analyses demonstrated the robustness of the results.ConclusionThe findings of this study provided no evidence to support that IBD has a large effect on risk of CVD outcomes, which is in contrast to many previous observational reports. Further studies are needed to determine the potential mechanism of association identified in observational studies.
| S-EPMC9478388 | biostudies-literature
Project description:BackgroundThe causal relationship between childhood obesity and hypertension in pregnancy remains unclear. To examine the causal association between childhood obesity and hypertension in pregnancy, two-sample Mendelian randomization analysis was applied.MethodsSingle-nucleotide polymorphisms (SNPs) associated with childhood obesity were obtained from a published genome-wide association study (GWAS) of 13 848 European individuals. Summary-level data for hypertension in pregnancy were obtained from the FinnGen consortium (11534 cases and 162212 controls). Inverse-variance weighted analysis, weighted-median analysis, and Mendelian randomization-Egger regression were conducted in this Mendelian randomization analysis. Sensitivity analyses were conducted to confirm the accuracy and robustness of our results.ResultsGenetically determined childhood obesity significantly affects hypertension in pregnancy by IVW [odds ratio (OR) = 1.161, 95% confidence interval (CI) 1.086-1.039; P = 9.92 × 10 -6 ] and weighted median (OR = 1.123, 95% CI 1.038-1.214; P = 0.004). These results were validated by multiple sensitivity analyses.ConclusionA causal effect between genetically predicted childhood obesity and the risk of hypertension in pregnancy was identified. The prevention of hypertension in pregnancy should be promoted in populations with childhood obesity.
| S-EPMC10241434 | biostudies-literature
Project description:AbstractMotivationIn recent years, Mendelian randomization analysis using summary data from genome-wide association studies has become a popular approach for investigating causal relationships in epidemiology. The mrrobust Stata package implements several of the recently developed methods.Implementationmrrobust is freely available as a Stata package.General featuresThe package includes inverse variance weighted estimation, as well as a range of median, modal and MR-Egger estimation methods. Using mrrobust, plots can be constructed visualizing each estimate either individually or simultaneously. The package also provides statistics such as IGX2, which are useful in assessing attenuation bias in causal estimates.AvailabilityThe software is freely available from GitHub [https://raw.github.com/remlapmot/mrrobust/master/].
| S-EPMC6659377 | biostudies-other
Project description:BackgroundAlthough observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous.MethodsWe conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis.ResultsResults from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06-1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04-1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02-1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes.ConclusionsThis MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.
| S-EPMC10475993 | biostudies-literature
Project description:BackgroundAlthough observational studies suggest a correlation between psoriasis (PS) and cancers, it is still unknown whether this association can replace causal relationships due to the limitations of observational studies. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between PS and cancers.MethodsPS genetic summary data were obtained from two genome-wide association studies (GWAS). We employed MR Base for individuals retrieving tumors from distinct locations. Inverse-variance weighted analysis was the principal method used for MR, supplemented by weighted median, MR Egger, simple mode, and weighted mode. To investigate the possible link between psoriasis and cancers, we performed two independent two-sample MR studies and a meta-analysis based on two independent MR analyses.ResultsTwo independent MR analyses both found no significant causal relationship between PS and overall cancers (OR=1.0000, 95% confidence interval [CI]:0.9999-1.0001, P=0.984; OR=1.0000, 95% CI:0.9999-1.0001, P=0.761), and no significant causal relationship with 17 site-specific cancers. In the meta-analysis conducted by two two-sample MR analyses, there was no significant causal relationship between PS and overall cancers (OR=1.0000, 95% CI: 0.9999-1.0001, P=1.00, I 2 = 0.0%), and there was no significant causal relationship with 17 site-specific cancers.ConclusionsOur findings do not support a genetic link between PS and cancers. More population-based and experimental investigations will be required better to understand the complicated relationship between PS and cancers.
| S-EPMC10991695 | biostudies-literature
Project description:BackgroundThere is a close clinical association between hypothyroidism and nephrotic syndrome (NS) was close, but whether there is genetic causality between the two is not known.ObjectiveUsing pooled data from a genome-wide association study (GWAS), the association between hypothyroidism and NS was explored via Mendelian randomization (MR) analysis.MethodsSingle-nucleotide polymorphisms (SNPs) associated with hypothyroidism (or NS) were screened as genetic instrumental variables (IVs) from pooled GWAS data, and inverse-variance weighting (IVW) was used for the main analysis to estimate causal effects, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept, MR-PRESSO and leave-one-out, were also conducted to assess the robustness of the results.ResultsGenetically predicted hypothyroidism was positively associated with the risk of developing NS (IVW: OR = 1.18, 95% CI: 1.07-1.30, p = 0.00; MR-Egger: OR = 1.36, 95% CI: 1.10-1.68, p = 0.01), and the MR-Egger intercept (intercept = -0.02, p = 0.14), MR-PRESSO test (p = 0.14), Cochran's Q test (p = 0.15) and leave-one-out test results supported the robustness of the results. Genetically predicted NS status might not be associated with an increased risk of developing hypothyroidism (IVW: OR = 1.01, 95% CI: 1.00-1.03, p = 0.08; MR-Egger: OR = 1.01, 95% CI: 0.98-1.04, p = 0.43), and the MR-Egger intercept (intercept < 0.01, p = 0.69), MR-PRESSO test (p = 0.64), Cochran's Q test (p = 0.61) and leave-one-out test results supported the robustness of the results.ConclusionHypothyroidism status could increase the risk of developing NS.
| S-EPMC11328803 | biostudies-literature
Project description:BackgroundPrevious epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis.MethodsWe performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.ResultsGenetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn's disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method.ConclusionsThis study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.
| S-EPMC10318899 | biostudies-literature