Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study

He, Menghao; Xu, Chun; Yang, Renyi; Liu, Lijuan; Zhou, Desheng; Yan, Siyang

doi:10.3389/fgene.2024.1333454

Cited by 3 publications

(1 citation statement)

References 48 publications

(39 reference statements)

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“…The selection of instrumental variables necessitates adherence to several assumptions ( 26 ), to fulfill their relevance ( 27 ), we conducted an association analysis on 731 immune cell phenotypes and 1,400 plasma metabolites, uniformly applying a threshold of P<1×10 −5 ( 28 , 29 ). Subsequently, SNPs exhibiting linkage disequilibrium were filtered out using criteria of R^2<0.001 and Kb=10,000 ( 30 ), followed by the calculation of the F-statistic for the selected SNPs to eliminate weak instrumental variables.…”

Section: Methodsmentioning

confidence: 99%

Dissecting causal relationships between immune cells, plasma metabolites, and COPD: a mediating Mendelian randomization study

Cao,

Wu,

Fang

et al. 2024

Front. Immunol.

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ObjectiveThis study employed Mendelian Randomization (MR) to investigate the causal relationships among immune cells, COPD, and potential metabolic mediators.MethodsUtilizing summary data from genome-wide association studies, we analyzed 731 immune cell phenotypes, 1,400 plasma metabolites, and COPD. Bidirectional MR analysis was conducted to explore the causal links between immune cells and COPD, complemented by two-step mediation analysis and multivariable MR to identify potential mediating metabolites.ResultsCausal relationships were identified between 41 immune cell phenotypes and COPD, with 6 exhibiting reverse causality. Additionally, 21 metabolites were causally related to COPD. Through two-step MR and multivariable MR analyses, 8 cell phenotypes were found to have causal relationships with COPD mediated by 8 plasma metabolites (including one unidentified), with 1-methylnicotinamide levels showing the highest mediation proportion at 26.4%.ConclusionWe have identified causal relationships between 8 immune cell phenotypes and COPD, mediated by 8 metabolites. These findings contribute to the screening of individuals at high risk for COPD and offer insights into early prevention and the precocious diagnosis of Pre-COPD.

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Section: Methodsmentioning

confidence: 99%

Dissecting causal relationships between immune cells, plasma metabolites, and COPD: a mediating Mendelian randomization study

Cao,

Wu,

Fang

et al. 2024

Front. Immunol.

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Untargeted metabolomics reveal signatures of a healthy lifestyle

Pathmasiri,

Rushing,

McRitchie

et al. 2024

Sci Rep

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This cross-sectional study investigated differences in the plasma metabolome in two groups of adults that were of similar age but varied markedly in body composition and dietary and physical activity patterns. Study participants included 52 adults in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females). The results using an extensive untargeted ultra high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolomics analysis with 10,535 metabolite peaks identified 486 important metabolites (variable influence on projections scores of VIP ≥ 1) and 16 significantly enriched metabolic pathways that differentiated LIFE and CON groups. A novel metabolite signature of positive lifestyle habits emerged from this analysis highlighted by lower plasma levels of numerous bile acids, an amino acid profile characterized by higher histidine and lower glutamic acid, glutamine, β-alanine, phenylalanine, tyrosine, and proline, an elevated vitamin D status, higher levels of beneficial fatty acids and gut microbiome catabolism metabolites from plant substrates, and reduced levels of N-glycan degradation metabolites and environmental contaminants. This study established that the plasma metabolome is strongly associated with body composition and lifestyle habits. The robust lifestyle metabolite signature identified in this study is consistent with an improved life expectancy and a reduced risk for chronic disease.

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Genetic information supports a causal relationship between trace elements, inflammatory proteins, and COPD: evidence from a Mendelian randomization analysis

Cao,

Zhao,

et al. 2024

Front. Nutr.

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ObjectiveDietary factors and nutritional status may be among the risk factors for Chronic Obstructive Pulmonary Disease (COPD). There exists a certain correlation between trace elements and COPD. Through Mendelian Randomization (MR) analysis, we investigated the causal relationships between trace elements, inflammatory proteins, and COPD.MethodsWe employed MR, multivariable MR (MVMR), and two-step MR (TSMR) approaches to assess the causal links between 15 trace elements and COPD, with 91 inflammatory proteins serving as mediators to further elucidate the tripartite causal relationships.ResultsTrace elements such as Folate (OR = 1.293, 95%CI 1.027–1.628; p = 0.029), Vitamin D (OR = 1.331, 95%CI 1.071–1.654; p = 0.010), Vitamin B12 (OR = 1.424, 95%CI 1.108–1.828; p = 0.006), and Iron (OR = 0.741, 95%CI 0.580–0.946; p = 0.016) demonstrated causal relationships with COPD. No causal relationship was observed in reverse MR. After adjusting for BMI, Folate (OR = 1.633, 95%CI 1.098–2.429; p = 0.015), Iron (OR = 0.507, 95%CI 0.31–0.778; p = 0.001), and Vitamin D (OR = 1.511, 95%CI 1.029–2.217; p = 0.034) were identified as independent risk factors for COPD, whereas Vitamin B12 (OR = 1.118, 95%CI 0.751–1.666; p = 0.581) was not. Mediation analysis indicated that CDCP1 (5.76%) may play a mediating role between Iron and COPD.ConclusionTrace elements such as Folate, Vitamin D, Vitamin B12, and Iron have causal relationships with COPD. After BMI adjustment, Folate, Vitamin D, and Iron emerge as independent risk factors. Furthermore, the inflammatory protein CDCP1 may partially mediate the causal relationship between Iron and COPD, offering a scientific basis for dietary recommendations that could benefit COPD patients. The supplementation of trace elements may be advantageous for individuals suffering from COPD.

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Causal relationship between human blood metabolites and risk of ischemic stroke: a Mendelian randomization study

Cited by 3 publications

References 48 publications

Dissecting causal relationships between immune cells, plasma metabolites, and COPD: a mediating Mendelian randomization study

Dissecting causal relationships between immune cells, plasma metabolites, and COPD: a mediating Mendelian randomization study

Untargeted metabolomics reveal signatures of a healthy lifestyle

Genetic information supports a causal relationship between trace elements, inflammatory proteins, and COPD: evidence from a Mendelian randomization analysis

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