scholarly journals Mendelian randomization reveals potential causal candidates for COVID-19 in 123 blood metabolites

2021 ◽  
Author(s):  
Shizheng Qiu ◽  
Donghua Wang ◽  
Yu Zhang ◽  
Yang Hu
Keyword(s):  
Mendelian Randomization ◽  
Blood Metabolites

scholarly journals Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Zixian Wang ◽  
Shiyu Chen ◽  
Qian Zhu ◽  
Yonglin Wu ◽  
Guifeng Xu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Human Blood ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Blood Metabolites ◽  
Causal Relationships

Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear.Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk.Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis.Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P < 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07–1.38]).Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention.

scholarly journals Assessing the Associations of Blood Metabolites With Osteoporosis: A Mendelian Randomization Study

2018 ◽  
Vol 103 (5) ◽  
pp. 1850-1855 ◽  
Author(s):  
Li Liu ◽  
Yan Wen ◽  
Lei Zhang ◽  
Peng Xu ◽  
Xiao Liang ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Blood Metabolites

scholarly journals Inter-determination of blood metabolite levels and gut microbiome supported by Mendelian randomization

2020 ◽  
Author(s):  
Xiaomin Liu ◽  
Xin Tong ◽  
Yuanqiang Zou ◽  
Xiaoqian Lin ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Genetic Information ◽  
Mendelian Randomization ◽  
The Other ◽  
Whole Body ◽  
Blood Metabolites ◽  
Whole Genome ◽  
Sequencing Data ◽  
Pectin Degradation

AbstractThe gut microbiome has been implicated in a variety of physiological states. Controversy over causality, however, has always haunted microbiome studies. Here, we utilized the bidirectional Mendelian randomization (MR) approach to address questions that are not yet mature for more costly randomized interventions. From a total of 3,432 Chinese individuals with shotgun sequencing data for whole genome and whole metagenome, as well as anthropometric and blood metabolic traits, we identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 out of the 58. Gut microbiome could determine features in the blood. For example, increased fecal relative abundances of Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration, and fecal microbial module pectin degradation might increase serum uric acid. On the other hand, blood features may determine gut microbial features, e.g. glutamic acid appeared to decrease Oxalobacter, and a few members of Proteobacteria were unidirectionally influenced by cardiometabolically important metabolites such as 5-methyltetrahydrofolic acid, alanine, as well as selenium. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies. The results are consistent with whole-body cross-talks of the microbiome and the circulating molecules.

Investigating Causality Between Blood Metabolites and Emotional and Behavioral Responses to Traumatic Stress: a Mendelian Randomization Study

2019 ◽  
Vol 57 (3) ◽  
pp. 1542-1552
Author(s):  
Carolina Muniz Carvalho ◽  
Frank R. Wendt ◽  
Dan J. Stein ◽  
Murray B. Stein ◽  
Joel Gelernter ◽  
...  
Keyword(s):  
Traumatic Stress ◽  
Mendelian Randomization ◽  
Behavioral Responses ◽  
Blood Metabolites

Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome

2022 ◽  
Author(s):  
Xiaomin Liu ◽  
Xin Tong ◽  
Yuanqiang Zou ◽  
Xiaoqian Lin ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Mendelian Randomization ◽  
Blood Metabolites ◽  
Causal Relationships

scholarly journals Mendelian randomization identifies the potential causal impact of dietary patterns on circulating blood metabolites

2020 ◽  
Author(s):  
Nele Taba ◽  
Hanna-Kristel Valge ◽  
Andres Metspalu ◽  
Tõnu Esko ◽  
James F. Wilson ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Principal Component ◽  
Blood Metabolites ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Nucleotide Polymorphisms ◽  
Ldl Particles ◽  
Effect Of Food

AbstractNutrition plays an important role in the development and progress of several health conditions, but the exact mechanism is often still unclear. Blood metabolites are likely candidates to be mediating these relationships, as their levels are strongly dependent on the frequency of consumption of several foods/drinks. Understanding the causal effect of food on metabolites is thus of extreme importance. To establish these effects we utilized Two-sample Mendelian randomization using the genetic variants associated with dietary traits as instrumental variables. The estimates of single-nucleotide polymorphisms’ effects on exposures were obtained from a recent genome-wide association study (GWAS) of 25 individual and 15 principal-component dietary traits, whereas the ones for outcomes were obtained from a GWAS of 123 blood metabolites measured by nuclear magnetic resonance spectroscopy. We identified 417 potentially causal links between food and metabolites, replicating previous findings, such as the association between increased oily fish consumption and higher DHA, and highlighting several novel associations. Most of the associations were related to very-low-density, intermediate-density (IDL) and low-density lipoproteins (LDL). For example, we found that constituents of IDL particles and large LDL particles were raised by coffee and alcohol while lowered by an overall healthier diet and fruit consumption. Our results represent one of the first examples of the estimates of long-term causal effects of diet on metabolites and start bridging the gap in the mechanistic understanding linking food consumption to its health consequences.

scholarly journals Genome-Wide Meta-Analysis and Mendelian Randomization Identify Early Biomarkers of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A315-A315
Author(s):  
Emilie Gobeil ◽  
Erik Abner ◽  
Nooshin Ghodsian ◽  
Nele Taba ◽  
Alexis St-Amand ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Blood Metabolites ◽  
Blood Proteins ◽  
Alcoholic Fatty Liver ◽  
Early Biomarkers ◽  
Genome Wide ◽  
Alcoholic Fatty Liver Disease

Abstract Background: The diagnosis of non-alcoholic fatty liver disease (NAFLD) is often challenging. Blood-based biomarkers which are causally influenced by NAFLD and that are not modulated by secondary non-causal pathways, are promising candidates for the identification of patients with NAFLD. Objectives: To identify blood metabolites and blood proteins that are causally impacted by the presence of NAFLD using Mendelian randomization (MR). Methods: We created a NAFLD genetic instrument through the identification of independent single-nucleotide polymorphisms associated with NAFLD in a meta-analysis of genome-wide association studies (GWAS) (6715 cases and 682,748 controls). Using inverse-variance weighted MR, we investigated the impact of NAFLD on 123 blood metabolites (in 24,925 participants from 10 European cohorts) and 3283 blood proteins (in 3301 participants from the INTERVAL cohort). Results: Our genetic instrument for genetically predicted NAFLD included 12 SNPs at the MTARC1, GCKR, LPL, TRIB1, LMO3, FTO, TM6SF2, APOE and PNPLA3 loci. After correction for false-discovery rate, we found a positive effect of NAFLD on blood tyrosine levels and on blood levels of eight proteins (encoded by the IDUA, ADH4, HMGCS1, GSTA1, ASL, POR, FBP1 and CTSZ genes). These association were robust to outliers and we found to evidence of horizontal pleiotropy. Conclusions: We report the existence of a potentially causal impact of the presence of NAFLD on tyrosine metabolism as well as on eight circulating proteins, which could potentially represent early biomarkers of NAFLD.

scholarly journals Metabolome-Wide Mendelian Randomization Analysis of Emotional and Behavioral Responses to Traumatic Stress

2019 ◽  
Author(s):  
Carolina Muniz Carvalho ◽  
Frank R. Wendt ◽  
Dan J. Stein ◽  
Murray B. Stein ◽  
Joel Gelernter ◽  
...  
Keyword(s):  
Traumatic Stress ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Behavioral Responses ◽  
Traumatic Experience ◽  
Blood Metabolites ◽  
Very Low Density Lipoproteins ◽  
Genome Wide ◽  
Stressful Experience ◽  
Trauma Response

AbstractTrauma exposure is an important risk factor for several psychiatric disorders; however, the mechanisms that underlie emotional and behavioral responses to traumatic stress are unclear. To understand these mechanisms, this study investigated the genetic overlap and causal relationship between blood metabolites and traits related to trauma response using genome-wide data. Five traits related to trauma response “in the past month” ascertained in the UK Biobank (52 816<N<117 900 individuals) were considered: i) “Avoided activities or situations because of previous stressful experience” (Avoidance); ii) “Felt distant from other people” (Distant); iii) “Felt irritable or had angry outbursts” (Irritable); iv) “Felt very upset when reminded of stressful experience” (Upset); v) “Repeated disturbing thoughts of stressful experience” (Repeated Thoughts). These were investigated with respect to 52 metabolites assessed using nuclear magnetic resonance metabolomics in a previous genome-wide association study (up to 24,925 individuals of European descent). Applying linkage disequilibrium score regression (LDSC), polygenic risk scoring (PRS), and Mendelian randomization (MR), we observed that 14 metabolites were significantly correlated with trauma response traits (p<0.05); PRS of 4 metabolites (citrate (CIT); glycoprotein acetyls (GP); concentration of large very-low-density lipoproteins (VLDL) particles (LVLDLP); total cholesterol in medium particles of VLDL (MVLDLC)) were associated with traits related to trauma response (false discovery rate Q<10%). These associations were partially due to causal relationships (CIT→Upset β=-0.058, p=9.1×10−4; GP→Avoidance β=0.008, p=0.003; LVLDLP→Distant β=0.008, p=0.022; MVLDLC→Avoidance β=0.019, p=3×10−4). No reverse associations were observed. In conclusion, the genetics of certain blood-metabolites are potentially implicated in the response to traumatic experience.

scholarly journals The relationship between blood metabolites of the tryptophan pathway and kidney function: a bidirectional Mendelian randomization analysis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yurong Cheng ◽  
Yong Li ◽  
Paula Benkowitz ◽  
Claudia Lamina ◽  
Anna Köttgen ◽  
...  
Keyword(s):  
Kidney Function ◽  
Mendelian Randomization ◽  
Blood Metabolites ◽  
Mendelian Randomization Analysis ◽  
Tryptophan Pathway ◽  
The Relationship ◽  
Randomization Analysis

scholarly journals Mendelian Randomization Identifies the Potential Causal Impact of Dietary Patterns on Circulating Blood Metabolites

2021 ◽  
Vol 12 ◽  
Author(s):  
Nele Taba ◽  
Hanna-Kristel Valge ◽  
Andres Metspalu ◽  
Tõnu Esko ◽  
James F. Wilson ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Principal Component ◽  
Blood Metabolites ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Nucleotide Polymorphisms ◽  
Strong Base ◽  
Ldl Particles

Nutrition plays an important role in the development and progress of several health conditions, but the exact mechanism is often still unclear. Blood metabolites are likely candidates to be mediating these relationships, as their levels are strongly dependent on the frequency of consumption of several foods/drinks. Understanding the causal effect of food on metabolites is thus of extreme importance. To establish these effects, we utilized two-sample Mendelian randomization using the genetic variants associated with dietary traits as instrumental variables. The estimates of single-nucleotide polymorphisms’ effects on exposures were obtained from a recent genome-wide association study (GWAS) of 25 individual and 15 principal-component dietary traits, whereas the ones for outcomes were obtained from a GWAS of 123 blood metabolites measured by nuclear magnetic resonance spectroscopy. We identified 413 potentially causal links between food and metabolites, replicating previous findings, such as the association between increased oily fish consumption and higher DHA, and highlighting several novel associations. Most of the associations were related to very-low-density, intermediate-density (IDL), and low-density lipoproteins (LDL). For example, we found that constituents of IDL particles and large LDL particles were raised by coffee and alcohol while lowered by an overall healthier diet and fruit consumption. Our findings provide a strong base of evidence for planning future RCTs aimed at understanding the role of diet in determining blood metabolite levels.

Sign in / Sign up

Export Citation Format

Share Document