Dataset Information

Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study.

ABSTRACT: Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly available summary-level datasets from GWAS consortia on apoA-IV concentrations (n?=?13,813), kidney function (estimated glomerular filtration rate (eGFR), n?=?133,413), lipid traits (HDL cholesterol, LDL cholesterol, triglycerides, n?=?188,577), adiposity-related traits (body-mass-index (n?=?322,206), waist-hip-ratio (n?=?210,088)) and fasting glucose (n?=?133,010). Main analyses consisted in inverse-variance weighted and multivariable MR, whereas MR-Egger regression and weighted median estimation were used as sensitivity analyses. We found that eGFR is likely to be causal on apoA-IV concentrations (53 SNPs; causal effect estimate per 1-SD increase in eGFR?=?-0.39; 95% CI?=?[-0.54, -0.24]; p-value?=?2.4e-07). Triglyceride concentrations were also causally associated with apoA-IV concentrations (40 SNPs; causal effect estimate per 1-SD increase in triglycerides?=?-0.06; 95% CI?=?[-0.08, -0.04]; p-value?=?4.8e-07), independently of HDL-C and LDL-C concentrations (causal effect estimate from multivariable MR?=?-0.06; 95% CI?=?[-0.10, -0.02]; p-value?=?0.0014). Evaluating the inverse direction of causality revealed a possible causal association of apoA-IV on HDL-cholesterol (2 SNPs; causal effect estimate per one percent increase in apoA-IV?=?-0.40; 95% CI?=?[-0.60, -0.21]; p-value?=?5.5e-05).

SUBMITTER: Mack S

PROVIDER: S-EPMC5562707 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study.

Mack Salome S Coassin Stefan S Vaucher Julien J Kronenberg Florian F Lamina Claudia C

Scientific reports 20170818 1

Apolipoprotein A-IV (apoA-IV) has been observed to be associated with lipids, kidney function, adiposity- and diabetes-related parameters. To assess the causal relationship of apoA-IV with these phenotypes, we conducted bidirectional Mendelian randomization (MR) analyses using publicly available summary-level datasets from GWAS consortia on apoA-IV concentrations (n = 13,813), kidney function (estimated glomerular filtration rate (eGFR), n = 133,413), lipid traits (HDL cholesterol, LDL cholester ...[more]

PMID: 28821713

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Project description:BackgroundGrowing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional.MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method.ResultsIn the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found.ConclusionOur study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

Dataset Information

Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study.

Publications

Evaluating the Causal Relation of ApoA-IV with Disease-Related Traits - A Bidirectional Two-sample Mendelian Randomization Study.

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