Gut microbiome and risk of ischaemic stroke: a comprehensive Mendelian randomization study

Meng, Changjiang; Deng, Peizhi; Miao, Rujia; Tang, Haibo; Li, Yalan; Wang, Jie; Wu, Jingjing; Wang, Wei; Liu, Shiqi; Xia, Jian; Lu, Yao

doi:10.1093/eurjpc/zwad052

Cited by 42 publications

(27 citation statements)

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“…Second, we must establish that there is no relationship between exposure-related genetic variants and outcomes. Finally, the third assumption assumes that these variants should not be correlated with any confounding variables [22,23].…”

Section: Assumption Of Mendelian Randomizationmentioning

confidence: 99%

Association between gut microbiota and psoriasis: a bidirectional two-sample Mendelian randomization study

Zhang,

Xiang,

Shen

et al. 2023

Preprint

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Background: Research has found that the composition of gut microbiota is related to psoriasis and its subtypes. However, the causal effect of gut microbiota on psoriasis is still unclear. Methods: A two sample Mendelian randomization randomized study was conducted using the aggregated statistical data of intestinal microbiota in the meta-analysis of the largest available genome-wide association studies conducted by the MiBioGen Alliance. The summary statistical data for psoriasis, arthropathic psoriasis, and psoriasis vulgaris are from the FinnGen Alliance R7 release. Reverse variance weighting, maximum likelihood, MR Egger, weighted median, weighted model, MR-PRESSO, and cML MA were used to examine the causal relationship between gut microbiota and psoriasis, arthropathic psoriasis, and psoriasis vulgaris. In the forward Mendelian randomization randomization analysis, reverse Gregor Mendel randomization analysis was performed on bacteria found to have causal relationships with psoriasis, arthropathic psoriasis and psoriasis vulgaris. Cochran's Q statistics are used to quantify the heterogeneity of Instrumental variables estimation. Results: A higher genetically predicted abundance Odoribacter was associated with a reduced risk of psoriasis. While a higher genetically predicted abundance of Ruminiclostridium5 was associated with an increased risk of psoriasis. The genetically predicted relative abundance of Verrucomicrobiae, Verrucomicrobiaceae, Akkermansia, Verrucomicrobiales were positively associated with arthropathic psoriasis. A higher genetically predicted abundance of Rikenellaceae served as protective factors for arthropathic psoriasis. Specifically, a higher genetically predicted Atinomycetaceae, Eubacterium fissicatena group, Lactococcus, and Actinomycetales were associated with a higher risk of psoriasis vulgaris. In contrast, higher genetically predicted Odoribacter was a lower risk of psoriasis vulgaris. No significant heterogeneity or level pleiotropy of Instrumental variables estimation was found. Conclusion: This MR study offer novel perspectives regarding the prevention, advancement, and therapy of psoriasis by concentrating on specific bacterial groups. Additional research is required to specify the exact mechanism relating the association between gut microbiota and psoriasis along with its classifications.

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Section: Assumption Of Mendelian Randomizationmentioning

confidence: 99%

Association between gut microbiota and psoriasis: a bidirectional two-sample Mendelian randomization study

Zhang,

Xiang,

Shen

et al. 2023

Preprint

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“…Second, the appropriate IVs were subjected to MR analysis. Sensitivity analysis was conducted to verify these results ( 18 , 19 ).…”

Section: Methodsmentioning

confidence: 99%

“…As Genome-wide association studies (GWAS) have greatly improved, we can observe the genetic susceptibility to the gut microbiome and skin fibrosis ( 16 , 17 ). MR can be considered a new method for exploring the relationship between the gut microbiome and skin fibrosis ( 8 , 13 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of the gut microbiome on skin fibrosis: a Mendelian randomization study

Zhao,

Xu,

et al. 2024

Front. Med.

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ObjectiveSkin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis.MethodsWe retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results.ResultsAccording to the inverse variance-weighted estimation, we identified that ten bacterial traits (Class Actinobacteria, Class Bacteroidia, family Bifidobacteriaceae, family Rikenellaceae, genus Lachnospiraceae (UCG004 group), genus Ruminococcaceae (UCG013 group), order Bacteroidales, order Bifidobacteriales, genus Peptococcus and genus Victivallis) were negatively correlated with skin fibrosis while five bacterial traits (genus Olsenella, genus Oscillospira, genus Turicibacter, genus Lachnospiraceae (NK4A136group), and genus Sellimonas) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis.Objective conclusionThere is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.

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“…Secondly, the single nucleotide polymorphisms (SNPs) of genetic variants should be independent and unaffected by any confounding factors. Finally, IVs should in uence the outcomes solely through the exposure pathway, without any alternative pathways [14] . Utilizing these principles, causal links between exposures and outcomes are meticulously explored through both univariate and multivariate MR analyses, leveraging data from previously published large-scale GWAS.…”

Section: Methodsmentioning

confidence: 99%

Mendelian randomization analyses explore the relationship between cathepsins and stroke

Chen,

Jiang,

Shen

et al. 2023

Preprint

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Background：Our current understanding of cathepsins' role in stroke is limited. To delve deeper, we're using R software for bidirectional and multivariate Mendelian Randomization (MR) studies. Method：We used public Genome-Wide Association Studies (GWAS). Data on cathepsins (n=3,301) came from the INTERVAL study; stroke data (n=446,696) from the MEGASTROKE consortium, including ischemic stroke (IS) (n=440,328) and its subtypes, and intracerebral hemorrhage (ICH) (n=3,026). Our main analytical method was Inverse Variance Weighting (IVW). Supplementary methods included Weighted Median, MR-Egger, Simple Mode, and Weighted Mode. Heterogeneity was assessed via Cochran Q test, and pleiotropy through MR-Egger intercept and MR-PRESSO analysis. Leave-one-out analysis ensured result stability. Results：We detected that Cathepsin S acts as a protective factor against cardioembolic IS(IVW: p=0.014, odds ratio (OR) = 0.918, 95% confidence interval (CI) = 0.857-0.983).In the reverse causation analysis, we found a positive correlation between overall stroke and Cathepsin S (IVW: p=0.006, OR=1.509, 95%CI=1.128-2.019), IS and Cathepsin S (IVW: p=0.015, OR=1.368, 95%CI=1.063-1.762), and large artery IS and Cathepsin S (IVW: p=0.034, OR=1.225, 95%CI=1.015-1.479). Multivariable MR indicated a negative correlation between Cathepsin S and both cardioembolic IS (IVW: p=0.002, OR=0.889, 95%CI=0.825-0.958) and IS (IVW: p=0.032, OR=0.964, 95%CI=0.932-0.997), and between Cathepsin F and IS (IVW: p=0.040, OR=0.946, 95%CI=0.898-0.998). Conversely, Cathepsin E showed a positive correlation with small vessel IS (IVW: p=0.022, OR=1.155, 95%CI=1.021-1.307). Conclusion：This study provides genetic evidence that Cathepsin S may be a potential protective factor against cardioembolic IS. Further studies are required to elucidate the underlying mechanisms of this causal relationship.

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Gut microbiome and risk of ischaemic stroke: a comprehensive Mendelian randomization study

Cited by 42 publications

References 50 publications

Association between gut microbiota and psoriasis: a bidirectional two-sample Mendelian randomization study

Association between gut microbiota and psoriasis: a bidirectional two-sample Mendelian randomization study

Impact of the gut microbiome on skin fibrosis: a Mendelian randomization study

Mendelian randomization analyses explore the relationship between cathepsins and stroke

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