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 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 Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations

Diabetes Care ◽  
2020 ◽  
Vol 44 (1) ◽  
pp. 98-106
Author(s):  
Ju-Sheng Zheng ◽  
Jian’an Luan ◽  
Eleni Sofianopoulou ◽  
Fumiaki Imamura ◽  
Isobel D. Stewart ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin C ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Genome Wide Association ◽  
Plasma Vitamin ◽  
Genome Wide ◽  
Randomization Analysis ◽  
European Populations

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).

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.

Association Between Hemostatic Profile and Migraine: A Mendelian Randomization Analysis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011931
Author(s):  
Yanjun Guo ◽  
Pamela M. Rist ◽  
Maria Sabater Lleal ◽  
Paul de Vries ◽  
Nicholas Smith ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Coagulation Factor ◽  
Fibrinopeptide A ◽  
Genome Wide ◽  
Hemostatic Factors ◽  
Independent Effects ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Randomization Analysis

Objective:To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis.Methods:Two-sample Mendelian randomization (MR) instrumental leveraging available genome-wide association study (GWAS) summary statistics was applied to hemostatic measures as potential causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of eight hemostatic factors and two fibrinopeptides together with two hemostasis clinical tests.Results:There were significant instrumental effects between increased coagulation factor VIII activity (FVIII, OR [95% CI]=1.05[1.03, 1.08]/SD, P=6.08×10-05), von Willebrand factor level (VWF, 1.05[1.03, 1.08]/SD, P=2.25×10-06), and phosphorylated fibrinopeptide A level (1.13[1.07, 1.19]/SD, P=5.44×10-06) with migraine susceptibility. When extended to migraine subtypes, FVIII, VWF, and phosphorylated fibrinopeptide A showed slightly stronger effects with MA than overall migraine. Fibrinogen level was inversely linked with MA (0.76[0.64, 0.91]/SD, P=2.32×10-03) but not overall migraine. None of the hemostatic factors was linked with MO. In sensitivity analysis, effects for fibrinogen and phosphorylated fibrinopeptide A were robust, while independent effects of FVIII and VWF could not be distinguished, and FVIIII associations were potentially affected by pleiotropy at the ABO locus. Causal effects from migraine to the hemostatic measures were not supported in reverse MR. However, MA was not included due to lack of instruments.Conclusions:The findings support potential causality of increased FVIII, VWF, and phosphorylated fibrinopeptide A, and decreased fibrinogen in migraine susceptibility, especially for MA, potentially revealing etiologic relationships between hemostasis and migraine.

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