The causal associations between growth factors and constipation: a two-sample Mendelian randomization study

Wang, Jiachen; Yang, Mingyi; Xu, Ke; Wan, Xianjie; Xie, Jiale; Yu, Hui; Fang, Jiapeng; Qin, Yanru; Xu, Peng

doi:10.3389/fphys.2023.1204146

Cited by 4 publications

(2 citation statements)

References 51 publications

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“…R 2 was estimated via employing the equation: R 2 = 2 × MAF × (1 − MAF) × β 2 , where β is the allele effect value and MAF is the effect allele frequency. SNPs with an F-statistic greater than 10 were considered reliable IVs due to their ability to reduce bias associated with weak instruments in MR analyses [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis

Zhu,

Liu,

Peng

et al. 2024

Diabetol Metab Syndr

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Background The interplay between diabetes mellitus (DM), glycemic traits, and vascular and valvular calcifications is intricate and multifactorial. Exploring potential mediators may illuminate underlying pathways and identify novel therapeutic targets. Methods We utilized univariable and multivariable Mendelian randomization (MR) analyses to investigate associations and mediation effects. Additionally, the multivariable MR analyses incorporated cardiometabolic risk factors, allowing us to account for potential confounders. Results Type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c) were positively associated with both coronary artery calcification (CAC) and calcific aortic valvular stenosis (CAVS). However, fasting glucose (FG) was only linked to CAVS and showed no association with CAC. Additionally, CAVS demonstrated a causal effect on FG. Calcium levels partially mediated the impact of T2DM on both types of calcifications. Specifically, serum calcium was positively associated with both CAC and CAVS. The mediation effects of calcium levels on the impact of T2DM on CAC and CAVS were 6.063% and 3.939%, respectively. The associations between T2DM and HbA1c with calcifications were influenced by body mass index (BMI) and smoking status. However, these associations were generally reduced after adjusting for hypertension. Conclusion Our findings suggest a genetically supported causal relationship between DM, glycemic traits, and vascular and valvular calcifications, with serum calcium playing a critical mediating role.

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Section: Methodsmentioning

confidence: 99%

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis

Zhu,

Liu,

Peng

et al. 2024

Diabetol Metab Syndr

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“…[18], growth factor (GF) [19] have direct causal relationships with constipation. However, MR study of gut microbiota and constipation was not investigated yet.…”

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confidence: 99%

Causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study

He,

Li,

Zhang

et al. 2023

Preprint

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Background As one of the most common gastrointestinal disorders, recent study has shown that dysfunction in the gut microbiota might lead to constipation. However, the causality between the gut microbiota and constipation is unclear. Methods Genome-Wide Association Studies (GWAS) used to obtain the summary-level data of constipation through IEU OpenGWAS database, and constipation was used as outcome. In addition, MiBioGen was used to gain the summary data of gut microbiota, including Ruminiclostridium 9, Intestinibacter, Anaerotruncus, Butyricimonas and Hungatella, which were used as exposure factors. Univariable Mendelian randomization (MR) analysis was used to evaluate the causality of gut microbiota on constipation. In briefly, Inverse-variance weighted (IVW) method was regarded as a main method to estimate the causality of gut microbiota and constipation, and supplemented by other four methods, including MR-egger, Weighted median, Simple mode and Weighted mode. Finally, funnel plot, heterogeneity test, horizontal pleiotropy test and leave-one-out test were used to evaluate the reliability of MR results. Results Ruminiclostridium 9 and Intestinibacter were causally associated with constipation and were the protective factors for constipation based on the MR analysis of IVW. The causal odds ratio (OR) values of Ruminiclostridium 9 and Intestinibacter were 0.75 (95% confidence interval (CI) 0.73–0.78; P < 0.001) and 0.89 (95% CI 0.86–0.93; P < 0.001) for constipation. Moreover, Anaerotruncus, Butyricimonas and Hungatella were also causally associated with constipation but were the risk factors for constipation. The OR values of Anaerotruncus, Butyricimonas and Hungatella were 1.08 (95% CI 1.02–1.13; P = 0.007), 1.07 (95% CI 1.01–1.13; P = 0.015), 1.03 (95% CI 1.00-1.06; P = 0.037) respectively. Furthermore, validation by funnel plot, heterogeneity test and horizontal pleiotropy test showed that MR results were reliable. Conclusion Ruminiclostridium 9, Intestinibacter, Anaerotruncus, Butyricimonas and Hungatella were identified as causalities of constipation, which provided a basis for understanding pathology of constipation and new insights into prevention and treatment.

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Assessing the causal effects of Eubacterium and Rumphococcus on constipation: a Mendelian randomized study

Zhang,

Chen,

et al. 2024

Front. Microbiol.

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BackgroundConstipation is affected by a number of risk variables, including cardiovascular disease and growth factors. However, the impacts of gut flora on constipation incidence has not been shown. This work, Single-Variable Mendelian Randomization (SVMR) was utilized to estimate the causal relationship between the Eubacterium genus or Rumphococcus, and constipation.MethodsData for constipation, Eubacterium genus and Rumphococcus were taken from the Integrated Epidemiology Unit (IEU) open GWAS database. Including 218,792 constipation samples, and there were 16,380,466 Single Nucleotide Polymorphisms (SNPs) for constipation. The ids of Eubacterium genus and Rumphococcus were sourced from MiBioGen database. The sample count for the Eubacterium genus was 17,380, with 656 SNPs. In addition, the sample size for Rumphococcus was 15,339, with 545 SNPs. The SVMR was performed to assess the risk of Eubacterium genus and Rumphococcus in constipation using weighted median, MR Egger, simple mode, inverse variance weighted (IVW), and weighted mode. Finally, we did a sensitivity analysis that included a heterogeneity, horizontal pleiotropy, and Leave-One-Out (LOO) test to examine the viability of the MR data.ResultsThe SVMR revealed that the Eubacterium genus and Rumphococcus were causally connected to constipation, with Rumphococcus (P = 0.042, OR = 1.074) as a hazardous factor and Eubacterium genus (P = 0.004, OR = 0.909) as a safety factor. Sensitivity tests then revealed the absence of variability between the constipation and the exposure factors (Eubacterium genus and Rumphococcus). Additionally, there were no other confounding factors and the examined SNPs could only influence constipation through the aforementioned exposure factors, respectively. As a result, the MR results were fairly robust.ConclusionOur investigation verified the causal links between the Eubacterium genus or Rumphococcus, and constipation, with greater Rumphococcus expression increasing the likelihood of constipation and the opposite being true for the Eubacterium genus.

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The causal associations between growth factors and constipation: a two-sample Mendelian randomization study

Cited by 4 publications

References 51 publications

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis

Exploring the mediating role of calcium homeostasis in the association between diabetes mellitus, glycemic traits, and vascular and valvular calcifications: a comprehensive Mendelian randomization analysis

Causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study

Assessing the causal effects of Eubacterium and Rumphococcus on constipation: a Mendelian randomized study

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