scholarly journals A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1420 ◽  
Author(s):  
Iraia García-Santisteban ◽  
Ariadna Cilleros-Portet ◽  
Elisabet Moyua-Ormazabal ◽  
Alexander Kurilshikov ◽  
Alexandra Zhernakova ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Outcome Data ◽  
Nucleotide Polymorphisms ◽  
Mendelian Randomization Analysis ◽  
Immune Mediated ◽  
And Function ◽  
Randomization Analysis

Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by the ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculated that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a two-sample Mendelian randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous genome-wide association study (GWAS) of gut microbiota and outcome data from summary statistics of CeD GWAS and Immunochip studies. We identified a number of putative associations between gut microbiota single nucleotide polymorphisms (SNPs) associated with CeD. Regarding bacterial composition, most of the associated SNPs were related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we linked a number of SNPs to several bacterial metabolic pathways that seemed to be related to CeD. Overall, this study represented the first 2SMR approach to elucidate the relationship between microbiome and CeD.

scholarly journals A Two-Sample Mendelian Randomization Analysis Investigates Associations between Gut Microbiota and Celiac Disease

2020 ◽  
Author(s):  
Iraia García-Santisteban ◽  
Ariadna Cilleros-Portet ◽  
Elisabet Moyua-Ormazabal ◽  
Alexander Kurilshikov ◽  
Alexandra Zhernakova ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gut Microbiota ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Outcome Data ◽  
Mendelian Randomization Analysis ◽  
Genome Wide ◽  
Immune Mediated ◽  
And Function ◽  
Randomization Analysis

Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculate that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a Two-Sample Mendelian Randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous Genome Wide Association Study (GWAS) of gut microbiota, and outcome data from summary statistics of CeD GWAS and Immunochip studies. We have identified a number of putative associations between gut microbiota SNPs associated with CeD. Regarding bacterial composition, most of the associated SNPs are related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we have linked a number of SNPs to several bacterial metabolic pathways that seem to be related to CeD. Overall, this study represents the first 2SMR approach to elucidate the relationship between microbiome and CeD.

scholarly journals Mendelian randomization analysis of Circulating adiponectin levels on prostate cancer

2021 ◽  
Author(s):  
Liangliang Ren ◽  
Chenhao Yu ◽  
Zhenwei Zhou ◽  
Gonghui Li
Keyword(s):  
Prostate Cancer ◽  
Protective Effect ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Causal Effects ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

Abstract Background: Previous observational studies showed a conflict with the correlation between circulating adiponectin levels and prostate cancer. Methods: In this study, we employed Mendelian randomization analysis to identify the causal effects between them. 14 single nucleotide polymorphisms were screened from the largest-scale genome-wide association study meta-analysis of adiponectin in a multi-ethnic population. The SNP outcome effects were obtained from Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome and Japanese Encyclopedia of Genetic Associations by Riken. Inverse variance weighted model with random-effects was the main effect estimation in our study, alongside weighted median, MR-Egger, and weighted mode models.Results: The results showed no significant causal estimate but a potential protective effect of adiponectin on prostate cancer. In addition, two other research of adiponectin repeated the analysis to avoid the bias of human species showing the similar results. Conclusion: Our study did not provide significant evidence to support the causal effects of circulating adiponectin levels on prostate cancer, but most of our results showed a potential protective effect requiring larger-scale MR analysis to confirm.

scholarly journals Observational and Causal Association of Blood Vitamin D with Gut Microbiota: Evidence from a Prospective Cohort and Mendelian Randomization Analysis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1513-1513
Author(s):  
Ju-Sheng Zheng ◽  
Xu Fengzhe ◽  
Yu-Ming Chen
Keyword(s):  
Vitamin D ◽  
Gut Microbiota ◽  
Prospective Cohort ◽  
Mendelian Randomization ◽  
Vitamin D Status ◽  
Causal Association ◽  
Mendelian Randomization Analysis ◽  
Prospective Association ◽  
Randomization Analysis ◽  
Microbiota Diversity

Abstract Objectives Little is known about the relationship between blood vitamin D status and gut microbiota. We aimed to investigate the prospective association of blood 25-hydroxyvitamin D (25(OH)D) with gut microbiota and assess their potential causal relationship. Methods Our study was based on the Guangzhou Nutrition and Health Study, a community-based prospective cohort in China. We examined the prospective association of baseline 25(OH)D with gut microbiota diversity, composition and individual taxa (mean 4.3 years of follow-up) (n = 1757) using linear or logistic regression models. Using genetic variants as instrument variables, we used a Mendelian randomization analysis to assess the causal relationship between 25(OH)D and gut microbiota. Results Higher blood 25(OH)D levels were associated with higher alpha-diversity indicators: including Chao1 index, Shannon index and Observed OUTs index (all P < 0.01, comparing extreme quartiles (Q) of 25(OH)D). Significant difference (P < 0.01) in beta-diversity was also found between Q1 and Q4 of 25(OH)D. Meanwhile, high 25(OH)D (Q4 versus Q1) was prospectively associated with the gut enterotype (Prevotella) and with differences in 37 individual taxa of gut microbiota (P < 0.05). Mendelian randomization analysis suggested that higher 25(OH)D was causally associated with higher abundance of Erysipelotrichaceae and with presence of Rothia. Conclusions Blood vitamin D status is prospectively associated with future gut microbiota diversity and composition. Available evidence suggests a potential causal association of vitamin D with some gut bacteria, and more research is needed to confirm these results. Funding Sources National Natural Science Foundation of China (81,903,316, 81,773,416).

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

2021 ◽  
pp. 174749302110062
Author(s):  
Bin Yan ◽  
Jian Yang ◽  
Li Qian ◽  
Fengjie Gao ◽  
Ling Bai ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Visceral Adiposity ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Genetic Liability ◽  
A Genome ◽  
Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5×10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48×10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01×10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16×10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

Cigarette Smoking Behavior a Gateway to Opium Use Disorder: A Mendelian Randomization Analysis

2021 ◽  
Author(s):  
Abdolhalim Rajabi ◽  
Azadeh Shojaei ◽  
Leila Janani ◽  
Mojtaba Farjam ◽  
Hamid Reza Baradaran ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Mendelian Randomization ◽  
Smoking Behavior ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis ◽  
Opium Use

scholarly journals Contribution of Infectious Agents to the Development of Celiac Disease

2021 ◽  
Vol 9 (3) ◽  
pp. 547
Author(s):  
Daniel Sánchez ◽  
Iva Hoffmanová ◽  
Adéla Szczepanková ◽  
Věra Hábová ◽  
Helena Tlaskalová-Hogenová
Keyword(s):  
Celiac Disease ◽  
Intestinal Mucosa ◽  
Wheat Gluten ◽  
Small Intestinal Mucosa ◽  
Beneficial Effects ◽  
Immune Mediated ◽  
Healthy State ◽  
Food Antigens ◽  
Small Intestinal ◽  
And Function

The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.

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