Dataset Information

Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study.

ABSTRACT:

Purpose

Major depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them.

Methods

We performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiatric Genomics Consortium and UK Biobank. Information on VTE, deep vein thrombosis (DVT), and pulmonary embolism (PE) were obtained from the FinnGen Biobank. Inverse-variance weighting was used as the main analysis method. Other methods include weighted median, MR-Egger, Simple mode, and Weighted mode.

Results

Univariable MR analysis revealed no significant associations between MDD and VTE risk (odds ratio (OR): 0.936, 95% confidence interval (CI): 0.736-1.190, p = 0.590); however, after adjusting the potential relevant polymorphisms of body mass index and education, the multivariable MR analysis showed suggestive evidence of association between them (OR: 1.163, 95% CI: 1.004-1.346, p = 0.044). Univariable MR analysis also revealed significant associations between MDD and PE risk (OR: 1.310, 95% CI: 1.073-1.598, p = 0.008), but the association between them was no longer significant in MVMR analysis (p = 0.072). We found no significant causal effects between MDD and DVT risk in univariable or multivariable MR analyses. There was also no clear evidence showing the causal effects between VTE, PE, or DVT and MDD risk.

Conclusion

We provide suggestive genetic evidence to support the causal association between MDD and VTE risk. No causal associations were observed between VTE, PE, or DVT and MDD risk. Further validation of these associations and investigations of potential mechanisms are required.

SUBMITTER: Li HY

PROVIDER: S-EPMC11231919 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study.

Li Hong-Yan HY Wang Li-Hong LH Wang Jing J Wang Yong-Bo YB Wang Hai-Shan HS

Frontiers in genetics 20240625

<h4>Purpose</h4>Major depressive disorder (MDD) and venous thromboembolism (VTE) may be linked in observational studies. However, the causal association remains ambiguous. Therefore, this study investigates the causal associations between them.<h4>Methods</h4>We performed a two-sample univariable and multivariable bidirectional Mendelian randomization (MR) analysis to evaluate the associations between MDD and VTE. The summary genetic associations of MDD statistics were obtained from the Psychiat ...[more]

PMID: 38983268

Similar Datasets

Project description:BackgroundMajor depressive disorder (MDD) is a highly heterogeneous mental illness and a major public health problem worldwide. A large number of observational studies have demonstrated a clear association between MDD and coronary heart disease (CHD), and some studies have even suggested that the relationship is bidirectional. However, it was unknown whether any causal relationship existed between them and whether causality was bidirectional in such an instance. Thus, we aimed to determine whether there is a bidirectional causal relationship between major depressive disorders and coronary heart disease.MethodsOur two-sample Bidirectional Mendelian Randomization Study consisted of two parts: forward MR analysis regarded MDD as exposure and CHD as the outcome, and reverse MR analysis considered CHD as exposure and MDD as the outcome. Summary data on MDD and CHD were obtained from the IEU Open GWAS database. After screening criteria(P < [Formula: see text]), 47 MDD-associated SNPs and 39 CHD-associated SNPs were identified. The inverse-variance weighted (IVW) method, ME-Egger regression, and weighted median method were used to estimate causality. In addition, sensitivity methods, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out method, were applied to ensure the robustness of causal estimation.ResultsBased on the MR-Egger regression intercept test results, there did not appear to be any horizontal pleiotropy in this study (MDD: intercept = -0.0000376, P = 0.9996; CHD: intercept = -0.0002698, P = 0.920). Accordingly, IVW results suggested consistent estimates of causal effect values. The results showed that people with MDD increased the risk of CHD by 14.7% compared with those without MDD (OR = 1.147, 95%CI: 1.045-1.249, P = 0.009). But there was no direct evidence that CHD would increase the risk of MDD(OR = 1.008, 95%CI: 0.985-1.031, P = 0.490). The heterogeneity test and funnel plot showed no heterogeneity in 47 SNPs of MDD (Q = 42.28, [Formula: see text]=0, P = 0.629), but there was heterogeneity in 39 SNPs of CHD (Q = 62.48, [Formula: see text]=39.18%, P = 0.007). The leave-one-out method failed to identify instances where a single SNP was either biased toward or dependent on the causation.ConclusionOur study supports a one-way causal relationship between MDD and CHD, but there is no bidirectional causal relationship. MDD increases the risk of CHD, but there is no evidence that CHD increases the risk of MDD. Therefore, the influence of psychological factors should also be considered in the prevention and treatment of CHD. For MDD patients, it is necessary to prevent cardiovascular diseases.

Project description:BackgroundObservational research has found a bidirectional relationship between major depressive disorder and gastroesophageal reflux disease; however, the causal association of this relationship is undetermined.AimsA bidirectional Mendelian randomization study was performed to explore the causal relationships between major depressive disorder and gastroesophageal reflux disease.MethodsFor the instrumental variables of major depressive disorder and gastroesophageal reflux disease, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium (r2 ≤ 0.001) were selected from relevant genome-wide association studies, respectively, at the genome-wide significance level (p ≤ 5 × 10-8). We sorted summary-level genetic data for major depressive disorder, gastroesophageal reflux disease, gastroesophageal reflux disease without esophagitis, and reflux esophagitis from meta-analysis study of genome-wide association studies involving 173,005 individuals (59,851 cases and 113,154 non-cases), 385,276 individuals (80,265 cases and 305,011 non-cases), 463,010 individuals (4360 cases and 458,650 non-cases), and 383,916 individuals (12,567 cases and 371,349 non-cases), respectively.ResultsGenetic liability to major depressive disorder was positively associated with gastroesophageal reflux disease and its subtypes. Per one-unit increase in log-transformed odds ratio of major depressive disorder, the odds ratio was 1.31 (95% confidence interval [CI], 1.19-1.43; p = 1.64 × 10-8) for gastroesophageal reflux disease, 1.51 (95% CI, 1.15-1.98; p = 0.003) for gastroesophageal reflux disease without esophagitis, and 1.21 (95% CI, 1.05-1.40; p = 0.010) for reflux esophagitis. Reverse-direction analysis suggested that genetic liability to gastroesophageal reflux disease was causally related to increasing risk of major depressive disorder. Per one-unit increase in log-transformed odds ratio of gastroesophageal reflux disease, the odds ratio of major depressive disorder was 1.28 (95% confidence interval, 1.11-1.47; p = 1.0 × 10-3).ConclusionsThis Mendelian randomization study suggests a bidirectional causal relationship between major depressive disorder and gastroesophageal reflux disease.

Project description:Backgroundα-Klotho may involve in the occurrence and development of venous thromboembolism (VTE). However, the underlying relationship between circulating α-Klotho levels and VTE is still unclear.MethodsThis two-sample Mendelian Randomization (MR) study aims to explore the causal associations of circulating α-Klotho levels with different types of venous thromboembolism. Data of exposure and outcomes were extracted from the genome-wide association study (GWAS) of the MRC Integrative Epidemiology Unit (MRC-IEU). The fixed inverse variance weighted (IVW), MR-Egger, MR-Robust Adjusted Profile Score (RAPS) and the weighted-median methods were utilized to investigate the causal associations of circulating α-Klotho levels with different types of VTE. The effect size was expressed as odds ratios (ORs) and 95% confidence intervals (CIs), and the False Discovery Rate (FDR) test was used for correction. The MR scatter plot and leave-one-out test were used for sensitivity analysis. In addition, reverse causal associations were assessed.ResultsIVW estimates suggested that an elevated circulating α-Klotho level was associated with lower odds of deep vein thrombosis (DVT) of lower extremities (OR = 0.992, 95%CI: 0.986-0.998, P = 0.0074), pulmonary embolism (PE) (OR = 0.474, 95%CI: 0.255-0.881, P = 0.0183), and DVT of lower extremities combined with PE (OR = 0.984, 95%CI: 0.971-0.997, P = 0.0175). However, after the FDR correction, only negatively causal association between circulating α-Klotho level and increased odds of lower-extremity DVT was statistically significant (FDR P = 0.0296). Also, there were no reverse causal associations between the circulating α-Klotho levels and different types of VTE (all P > 0.05). Additionally, both the MR scatter plots and leave-one-out test results showed that these causal associations were relatively robust.ConclusionAn elevated circulating α-Klotho levels was associated with lower risk of DVT of lower extremities, PE, and DVT of lower extremities combined with PE, indicating α-Klotho has the potential to act as a target for early screening or treatment for VTE. However, the specific mechanism that α-Klotho influencing the occurrence of VTE still needed further exploration.

Dataset Information

Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study.

Purpose

Methods

Results

Conclusion

Publications

Causal association between major depressive disorder and venous thromboembolism: a bidirectional mendelian randomization study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets