The causal relationship between allergic diseases and heart failure: Evidence from Mendelian randomization study

Guo, Yan-Ge; Zhang, Yan; Liu, Weili

doi:10.1371/journal.pone.0271985

Cited by 8 publications

(5 citation statements)

References 61 publications

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“…To the best of our knowledge, this is the rst MR study to identify the bidirectional causal relationship between AD and CVD. A previous MR study has identi ed that asthma and atopic dermatitis are causal risk factors of heart failure (P = 0.03 and 0.01) [23]. The study could not illustrate the causal association between them after a Bonferroni correction.…”

Section: Discussionmentioning

confidence: 81%

Exploring genetic association of allergic disease with cardiovascular disease: A bidirectional Mendelian randomization study

Wang

Líu

Yang

et al. 2023

Preprint

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Background: In observational and experimental studies, allergic diseases have been reported to be associated with some types of cardiovascular diseases. They share a typical pathophysiological process, including inflammatory and metabolism disorders. However, the direction of the causal association between them remains unclear. This Mendelian randomization (MR) study aims to examine the bidirectional causality between allergic diseases and cardiovascular diseases. Methods:We used publicly available GWAS summary statistics data only, including European participants from UK Biobank or on the IEU Open GWAS database. We identified genetic variants associated with allergic diseases, asthma, or cardiovascular diseases as instrumental variables to investigate the genetically causal association between allergic diseases and asthma and the risk of 12 kinds of cardiovascular diseases. MR was performed using analytical methods including the inverse variance weighted (IVW), MR-Egger and, weighted median. Sensitivity tests were also performed in the MR to assess the validity of the casualty. Results: Genetically predicted allergic diseases was associated with essential hypertension [odds ratio (OR)=0.9987, 95% confidence interval (CI): 0.9976-0.9998, P=0.024], and asthma was associated with atherosclerosis (OR=1.0006, 95% CI: 1.0001-1.0012, P=0.02) in the MR analysis with the IVW method. In the reverse MR analyses, we found that essential hypertension was associated with allergic diseases (OR=8.16E-03, 95% CI: 7.55E-05 - 8,82E-01, P=0.044) and asthma (OR=8.16E-03, 95% CI: 7.55E-05 - 8,82E-01, P=0.044), and stroke was associated with allergic diseases (OR=3.59E-02, 95% CI: 1.34E-03 - 9.62E-01, P=0.047). However, no causal effect has been detected bidirectionally after the Bonferroni correction. Conclusion: The MR study found that patients with AD or asthma might have a decreased risk of essential hypertension and an increased risk of atherosclerosis in European individuals. In reverse analysis, essential hypertension, AD, and asthma are negatively correlated, and stroke may decrease the risk of AD. However, after a Bonferroni correction, our evidence did not suggest a significant causal between them, which means that the evidence is weak. Whether AD exerts effects on CVD needs further investigation.

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Section: Discussionmentioning

confidence: 81%

Exploring genetic association of allergic disease with cardiovascular disease: A bidirectional Mendelian randomization study

Wang

Líu

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…Aligned with current research standards, the threshold for the significance of IVs linked to each immune trait was set at 1×10-5 ( 20 – 23 ). To refine the selection of SNPs, we implemented a clumping procedure, applying a linkage disequilibrium (LD) r2 threshold of less than 0.001 within a 10,000 kb distance ( 24 – 26 ).…”

Section: Methodsmentioning

confidence: 99%

Unraveling the causal role of immune cells in gastrointestinal tract cancers: insights from a Mendelian randomization study

Wang,

Zhou,

Wang

et al. 2024

Front. Immunol.

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BackgroundDespite early attempts, the relationship between immune characteristics and gastrointestinal tract cancers remains incompletely elucidated. Hence, rigorous and further investigations in this domain hold significant clinical relevance for the development of novel potential immunotherapeutic targets.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis using the tools available in the “TwoSampleMR” R package. The GWAS data for these 731 immune traits were sourced from the GWAS Catalog database. Concurrently, data on gastrointestinal tract cancers, encompassing malignant tumors in the esophagus, stomach, small intestine, colon, and rectum, were extracted from the FinnGen database. The immune traits subjected to MR analysis predominantly fall into four categories: median fluorescence intensities (MFI), relative cell (RC), absolute cell (AC), and morphological parameters (MP). To ensure the reliability of our findings, sensitivity analyses were implemented to address robustness, account for heterogeneity, and alleviate the impact of horizontal pleiotropy.ResultsA total of 78 immune traits causally linked to gastrointestinal tract cancers were identified, encompassing esophageal cancer (12 traits), gastric cancer (13 traits), small intestine cancer (22 traits), colon cancer (12 traits), and rectal cancer (19 traits). Additionally, 60 immune traits were recognized as protective factors associated with gastrointestinal tract cancers, distributed across esophageal cancer (14 traits), gastric cancer (16 traits), small intestine cancer (7 traits), colon cancer (14 traits), and rectal cancer (9 traits). Furthermore, it was observed that seven immune traits are causally related to gastrointestinal tract cancers in at least two locations. These traits include “CCR2 on CD14- CD16+ monocyte,” “CD19 on IgD+ CD38-,” “CD19 on IgD+ CD38- naive,” “CD25hi CD45RA+ CD4 not Treg AC,” “CD27 on unsw mem,” “CD28 on CD39+ activated Treg,” and “CD45 on CD4+.”ConclusionThis study elucidates a causal link between immune cells and gastrointestinal tract cancers at various sites through genetic investigation. The findings of this research open up new perspectives and resources for exploring tumor prevention strategies and immunotherapeutic targets.

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“…We found that when we set the threshold of P at 5e-8, we got too few SNPs to support our further research. We set our threshold at 1e-5 with reference to the standards in previous studies (Yu et al, 2021;Guo et al, 2022;Wang and Zhang, 2024).…”

Section: Identification Of Instrumental Variablesmentioning

confidence: 99%

Causal effects and metabolites mediators between immune cell and risk of breast cancer: a Mendelian randomization study

Ming,

Wu,

Liu

et al. 2024

Front. Genet.

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Introduction: The incidence and mortality of female breast cancer remain high, and the immune microenvironment of breast cancer has undergone significant alterations. However, the impact of blood immune cell levels on the risk of breast cancer is not fully understood. Therefor this study aims to investigate the causal relationship between blood immune cell levels and the risk of breast cancer.Methods: A Mendelian randomization (MR) analysis was employed to assess the causal relationship between immune cells and the risk of breast cancer, as along with their potential mediating factors. Genetic statistics of metabolites breast cancer and immune cells were obtained from the GWAS Catalog, while the genome-wide association study (GWAS) statistics of breast cancer were extracted from the UK biobank. Two-sample MR analysis were performed using inverse-variance weighted (IVW) to ascertain the causal association between immune cells and the risk of breast cancer. Furthermore, 1,400 metabolites were analyzed for their mediating role between immune cells and the risk of breast cancer.Results: MR analysis through IVW method revealed that genetically predicted CD24+ CD27+ B cells were associated with a decreased risk of breast cancer (OR = 0.9978, 95% CI: 0.996–0.999, p = 0.001), while IgD- CD38+ B cells were linked to an increased risk of breast cancer (OR = 1.002, 95% CI: 1.001–1.004, p = 0.005). Additional CD14+ CD16+ monocytes were associated with an increased risk of breast cancer (OR = 1.000, 95% CI: 1.000–1.001, p = 0.005). Mediation analysis revealed a positive causal relationship between IgD- CD38+ B cells and Glycerate levels, with the latter also exhibiting a positive causal relationship with the risk of breast cancer (p < 0.05). Conversely, IgD- CD38+ B cells displayed a negative causal relationship with Succinoyltaurine levels, and the latter also demonstrated a negative causal relationship with the risk of breast cancer (p < 0.05).Conclusion: This MR study provides novel genetic evidence supporting a causal relationship between IgD- CD38+ B cells and the risk of BC. Moreover, it is identified that IgD- CD38+ B cells contribute to an increased risk of BC through both positive and negative mediation effects involving Glycerate and Succinoyltaurine.

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The causal relationship between allergic diseases and heart failure: Evidence from Mendelian randomization study

Cited by 8 publications

References 61 publications

Exploring genetic association of allergic disease with cardiovascular disease: A bidirectional Mendelian randomization study

Exploring genetic association of allergic disease with cardiovascular disease: A bidirectional Mendelian randomization study

Unraveling the causal role of immune cells in gastrointestinal tract cancers: insights from a Mendelian randomization study

Causal effects and metabolites mediators between immune cell and risk of breast cancer: a Mendelian randomization study

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