Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis

Liu, Kangcheng; Wu, Pengfei; Zou, Jing; Fan, Huimin; Hu, Hanying; Cheng, Yanhua; He, Fei; Liu, Jingying; You, Zhipeng

doi:10.1007/s00439-022-02514-0

Cited by 12 publications

(8 citation statements)

References 38 publications

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“…In the our primary analyses, GM taxa (genus Blautia , genus Erysipelotrichaceae UCG003 , genus Lachnospira , and family Christensenellaceae ) with too few IVs ( n < 3) and those that were unknown were excluded (Liu et al, 2022; Lord et al, 2021). We then proceeded to analyse the bidirectional causal associations between 192 known GM taxa (including 9 phyla, 16 classes, 20 orders, 31 families and 116 genera) and periodontitis.…”

Section: Resultsmentioning

confidence: 99%

Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral–gut and gut–oral axes through bidirectional Mendelian randomization

Chen,

Peng,

Wang

et al. 2023

J Clinic Periodontology

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AimThis Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis.Materials and MethodsWe used genetic instruments from the genome‐wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR‐Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q‐test was performed to detect heterogeneity. The MR‐Egger regression intercept and MR pleiotropy residual sum and outlier test (MR‐PRESSO) were conducted to test potential horizontal pleiotropy. Leave‐one‐out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta‐analysis.ResultsWe confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014.ConclusionsThe demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut–oral and oral–gut axes.

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Section: Resultsmentioning

confidence: 99%

Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral–gut and gut–oral axes through bidirectional Mendelian randomization

Chen,

Peng,

Wang

et al. 2023

J Clinic Periodontology

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“…Pool data for 9 phyla, 16 classes, 20 orders, 35 families, and 131 genera of gut microbiota were obtained [ 23 ]. Among the 211 gut microbiota taxa, the unknown gut microbiota taxa were excluded, and the 196 known taxa were eventually analyzed in the MR analysis [ 24 , 25 ]. The composition of gut microbiota was characterized by sequencing three variable regions (V1-V2, V3-V4, and V4) of the 16S rRNA gene.…”

Section: Methodsmentioning

confidence: 99%

Causal associations between gut microbiota, metabolites and asthma: a two-sample Mendelian randomization study

Li,

Zhang,

Tang

et al. 2024

BMC Pulm Med

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Background While several traditional observational studies have suggested associations between gut microbiota and asthma, these studies are limited by factors such as participant selection bias, confounders, and reverse causality. Therefore, the causal relationship between gut microbiota and asthma remains uncertain. Methods We performed two-sample bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota and asthma as well as its phenotypes. We also conducted MR analysis to evaluate the causal effect of gut metabolites on asthma. Genetic variants for gut microbiota were obtained from the MiBioGen consortium, GWAS summary statistics for metabolites from the TwinsUK study and KORA study, and GWAS summary statistics for asthma from the FinnGen consortium. The causal associations between gut microbiota, gut metabolites and asthma were examined using inverse variance weighted, maximum likelihood, MR-Egger, weighted median, and weighted model and further validated by MR-Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis. Results We identified nine gut microbes whose genetically predicted relative abundance causally impacted asthma risk. After FDR correction, significant causal relationships were observed for two of these microbes, namely the class Bacilli (OR = 0.84, 95%CI = 0.76–0.94, p = 1.98 × 10−3) and the order Lactobacillales (OR = 0.83, 95%CI = 0.74–0.94, p = 1.92 × 10−3). Additionally, in a reverse MR analysis, we observed a causal effect of genetically predicted asthma risk on the abundance of nine gut microbes, but these associations were no longer significant after FDR correction. No significant causal effect of gut metabolites was found on asthma. Conclusions Our study provides insights into the development mechanism of microbiota-mediated asthma, as well as into the prevention and treatment of asthma through targeting specific gut microbiota.

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“…Valid MR is based on three assumptions ( 15 ), and the detailed principles are shown in Figure 1 . First, genetic variation is significantly associated with thyroid function; second, as an instrumental variable (IV) for exposure, the data should not be associated with the confounders of thyroid function and BPD; and, finally, BPD should only be influenced by genetic variation through thyroid function.…”

Section: Methodsmentioning

confidence: 99%

Genetically predicted alterations in thyroid function are associated with the risk of benign prostatic disease

et al. 2023

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BackgroundBenign prostatic diseases (BPDs), such as benign prostate hyperplasia (BPH) and prostatitis, harm the quality of life of affected patients. However, observational studies exploring the association between thyroid function and BPDs have hitherto yielded inconsistent results. In this study, we explored whether there is a causal genetic association between them using Mendelian randomization (MR) analysis.MethodsWe used publicly available summary statistics from the Thyroidomics Consortium and 23andMe on thyrotropin (TSH; 54,288 participants), thyroxine [free tetraiodothyronine (FT4); 49,269 participants], subclinical hypothyroidism (3,440 cases and 49,983 controls), overt hypothyroidism (8,000 cases and 117,000 controls), and subclinical hyperthyroidism (1,840 cases and 49,983 controls) to screen for instrumental variables of thyroid function. Results for BPD such as prostatic hyperplasia (13,118 cases and 72,799 controls) and prostatitis (1,859 cases and 72,799 controls) were obtained from the FinnGen study. The causal relationship between thyroid function and BPD was primarily assessed using MR with an inverse variance weighted approach. In addition, sensitivity analyses were performed to test the robustness of the results.ResultsWe found that TSH [OR (95% CI) = 0.912(0.845-0.984), p =1.8 x 10-2], subclinical hypothyroidism [OR (95% CI) = 0.864(0.810-0.922), p =1.04 x 10-5], and overt hypothyroidism [OR (95% CI) = 0.885 (0.831-0. 944), p =2 x 10-4] had a significant effect on genetic susceptibility to BPH, unlike hyperthyroidism [OR (95% CI) = 1.049(0.990-1.111), p =1.05 x 10-1] and FT4 [OR (95% CI) = 0.979(0.857-1.119), p = 7.59 x 10-1] had no effect. We also found that TSH [OR (95% CI) =0.823(0.700-0.967), p = 1.8 x 10-2] and overt hypothyroidism [OR (95% CI) = 0.853(0.730-0.997), p = 4.6 x 10-2] significantly influenced the prostatitis, whereas FT4 levels [OR (95% CI) = 1.141(0.901-1.444), p = 2.75 x 10-1], subclinical hypothyroidism [OR (95% CI) =0. 897(0.784- 1.026), p = 1.12 x 10-1], and hyperthyroidism [OR (95% CI) = 1.069(0.947-1.206), p = 2.79 x 10-1] did not have a significant effect.ConclusionOverall, our study results suggest that hypothyroidism and TSH levels influence the risk of genetically predicted BPH and prostatitis, providing new insights into the causal relationship between thyroid function and BPD.

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Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis

Cited by 12 publications

References 38 publications

Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral–gut and gut–oral axes through bidirectional Mendelian randomization

Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral–gut and gut–oral axes through bidirectional Mendelian randomization

Causal associations between gut microbiota, metabolites and asthma: a two-sample Mendelian randomization study

Genetically predicted alterations in thyroid function are associated with the risk of benign prostatic disease

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