Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study

Xia, Kailun; Wang, Yajun; Zhang, Linjing; Tang, Lu; Zhang, Gan; Huang, Tao; Huang, Ninghao

doi:10.3390/nu14050920

Cited by 16 publications

(13 citation statements)

References 80 publications

(85 reference statements)

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“…Serum LDL-C is a downstream product of the metabolism of PUFAs, and an association between PUFAs and ALS has been suggested previously [43]. Therefore, we further studied the possible mediation effect of LDL-C on the pathway from PUFAs to ALS.…”

Section: Discussionmentioning

confidence: 83%

Lipids and amyotrophic lateral sclerosis: A two‐sample Mendelian randomization study

Xia

Klose

Högel

et al. 2023

Euro J of Neurology

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Objective:Previous observational studies revealed a potential but partially controversial relation between lipid metabolism and the risk of amyotrophic lateral sclerosis (ALS), potentially prone to bias. Therefore, we aimed to study whether lipid metabolism involves genetically determined risk factors for ALS through Mendelian randomization (MR) analysis. Methods: Using genome-wide association study summary-level data for total cholesterol (TC) (n = 188,578), high-density lipoprotein cholesterol (HDL-C) (n = 403,943), low-density lipoprotein cholesterol (LDL-C) (n = 440,546), apolipoprotein A1 (ApoA1) (n = 391,193), apolipoprotein B (ApoB) (n = 439,214), and ALS (12,577 cases and 23,475 controls), we implemented a bidirectional MR study to evaluate a genetic relation between lipids and ALS risk. We performed a mediation analysis to assess whether LDL-C is a potential mediator on the pathway from traits of LDL-C-related polyunsaturated fatty acids (PUFAs) to ALS risk. Results:We identified genetically predicted increased lipid levels to be associated with the risk of ALS, whereby elevated LDL-C had the most potent effect (OR 1.028, 95% CI 1.008-1.049, p = 0.006). The effect of increased levels of apolipoproteins on ALS was similar to their corresponding lipoproteins. ALS did not cause any changes in lipid levels.We found no relation between LDL-C-modifying lifestyles and ALS. The mediation analysis revealed that LDL-C could act as an active mediator for linoleic acid, with the mediation effect estimated to be 0.009. Conclusions:We provided high-level genetic evidence verifying the positive link between preclinically elevated lipid and ALS risk that had been described in previous genetic and observational studies. We also demonstrated the mediating role of LDL-C in the pathway from PUFAs to ALS.

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Section: Discussionmentioning

confidence: 83%

Lipids and amyotrophic lateral sclerosis: A two‐sample Mendelian randomization study

Xia

Klose

Högel

et al. 2023

Euro J of Neurology

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“…To investigate the causal relationship for DE-FRGs and DE-ERGs with LUAD, MR analysis was executed to obtain candidate genes by TwoSampleMR function (v 0.5.7) (Xia et al 2022) with P < 5×10 -8 and Inverse variance weighted (IVW) (Burgess et al 2015) was the predominant method. The ieu-a-965 of LUAD was downloaded from Open GWAS database (https://gwas.mrcieu.ac.uk/).…”

Section: Mr Analysis To Obtain Candidate Genesmentioning

confidence: 99%

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

Zhang,

Hou,

Chen

et al. 2024

Preprint

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Background:Studies have demonstrated the prognostic potential of Epithelial-mesenchymal transition (EMT)-related genes (ERGs) and ferroptosis-related genes (FRGs) for Lung adenocarcinoma (LUAD) patients, but their correlation and underlying molecular mechanisms remain unknown. Thus, this investigation employs transcriptomics, Mendelian randomization (MR) analysis and single-cell data to explore the relationship and prognosis of EMT and ferroptosis with LUAD. Methods:Transcriptomic data from training and validation sets, along with single-cell datasets, were utilized. Prognostic-related differentially expressed (DE)-FRGs and DE-ERGs were identified, and a risk model was constructed using MR analysis and machine learning techniques. Single-cell data were analyzed to characterize model genes’ expression and function. Results:Totally, 40 DE-FRGs and 222 DE-ERGs related to prognostic were identified in TCGA-LUAD. And there were 7 candidate genes by MR analysis. A total of 6 model genes (TFAM, ALOX15, GATA1, ALAD, PDCD4 and NDRG2) were selected to construct a risk model and the model was verified by GSE11969. Meanwhile, stage, N, T, and risk score were screened out as independent prognostic factors via univariate and multivariate cox regression and scores were counted to build a nomogram. Then, MR analysis results revealed that 6 model genes were significantly causally associated with LUAD. Meanwhile, model genes were mainly enriched in NK cells, T cells, Endothelial cell clusters, etc. by single-cell analysis. Conclusion:TFAM, ALOX15, GATA1, ALAD, PDCD4 and NDRG2 played crucial roles in LUAD prognosis, providing refresh directions for the treatment of LUAD.

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“…Exposure factors were extracted and filtered using the "extract instruments" function of the TwoSampleMR package (17), with P < 5×10 −8 for forward and P < 5×10 −5 for reverse MR analyses. The initial analysis indicated that, using a strict threshold (P < 5×10 -8 ), the number of IVs was exceedingly limited.…”

Section: Data Pre-processingmentioning

confidence: 99%

Mendelian randomization and single-cell expression analyses identify the causal relationship between depression and chronic rhinosinusitis

Zhou,

Yang,

et al. 2024

Front. Psychiatry

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BackgroundThe causative relationship between chronic rhinosinusitis (CRS) and depression remains unclear. Herein we employed Mendelian randomization (MR) coupled with single-cell analysis to investigate the causality between CRS and depression.MethodsData pertaining to CRS and depression were mined from the genome-wide association study database, and a single-cell dataset was sourced from the literature. To explore causality, we conducted bidirectional MR analysis using MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode, with IVW representing the most important method. Further, sensitivity analysis was performed to evaluate the robustness of MR analysis results. Candidate genes were analyzed via single-cell combined MR analysis.ResultsForward MR analysis indicated depression as a risk factor for CRS when depression was the exposure factor and CRS was the outcome (OR = 1.425, P < 0.001). Reverse MR analysis revealed the same positive relationship between CRS and depression when CRS was the exposure factor and depression was the outcome (OR = 1.012, P = 0.038). Sensitivity analysis validated the robustness of bidirectional MR analysis results. Ten cell types (endothelial, ciliated, basal, myeloid, mast, apical, plasma, glandular, fibroblast, and T cells) were identified in the single-cell dataset. The network of receptor–ligand pairs showed that in normal samples, cell–cell interactions were present among various cell types, such as epithelial, mast, myeloid, and endothelial cells. In contrast, CRS samples featured only one specific receptor–ligand pair, confined to myeloid cells. TCF4 and MEF2C emerged as potentially crucial for CRS-associated depression development.ConclusionsOur findings suggest a bidirectional causal relationship between CRS and depression, offering a new perspective on the association between CRS and depression.

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Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study

Cited by 16 publications

References 80 publications

Lipids and amyotrophic lateral sclerosis: A two‐sample Mendelian randomization study

Lipids and amyotrophic lateral sclerosis: A two‐sample Mendelian randomization study

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

Mendelian randomization and single-cell expression analyses identify the causal relationship between depression and chronic rhinosinusitis

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