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- Burgess, S., et al.
(författare)
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Bayesian methods for meta-analysis of causal relationships estimated using genetic instrumental variables
- 2010
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Ingår i: Statistics in medicine. - : Wiley. - 1097-0258 .- 0277-6715. ; 29:12, s. 1298-311
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Tidskriftsartikel (refereegranskat)abstract
- Genetic markers can be used as instrumental variables, in an analogous way to randomization in a clinical trial, to estimate the causal relationship between a phenotype and an outcome variable. Our purpose is to extend the existing methods for such Mendelian randomization studies to the context of multiple genetic markers measured in multiple studies, based on the analysis of individual participant data. First, for a single genetic marker in one study, we show that the usual ratio of coefficients approach can be reformulated as a regression with heterogeneous error in the explanatory variable. This can be implemented using a Bayesian approach, which is next extended to include multiple genetic markers. We then propose a hierarchical model for undertaking a meta-analysis of multiple studies, in which it is not necessary that the same genetic markers are measured in each study. This provides an overall estimate of the causal relationship between the phenotype and the outcome, and an assessment of its heterogeneity across studies. As an example, we estimate the causal relationship of blood concentrations of C-reactive protein on fibrinogen levels using data from 11 studies. These methods provide a flexible framework for efficient estimation of causal relationships derived from multiple studies. Issues discussed include weak instrument bias, analysis of binary outcome data such as disease risk, missing genetic data, and the use of haplotypes.
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- Nieuwdorp, Max, et al.
(författare)
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Role of the microbiome in energy regulation and metabolism
- 2014
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Ingår i: Gastroenterology. - : W.B. Saunders. - 0016-5085 .- 1528-0012. ; 146:6, s. 1525-1533
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal microbes regulate metabolic function and energy balance; an altered microbial ecology is believed to contribute to the development of several metabolic diseases. Relative species abundance and metabolic characteristics of the intestinal microbiota change substantially in those who are obese or have other metabolic disorders and in response to ingested nutrients or therapeutic agents. The mechanisms through which the intestinal microbiota and its metabolites affect host homeostasis are just beginning to be understood. We review the relationships between the intestinal microbiota and host metabolism, including energy intake, use, and expenditure, in relation to glucose and lipid metabolism. These associations, along with interactions among the intestinal microbiota, mucus layer, bile acids, and mucosal immune responses, reveal potential mechanisms by which the microbiota affect metabolism. We discuss how controlled studies involving direct perturbations of microbial communities in human and animal models are required to identify effective therapeutic targets in the microbiota. © 2014 by the AGA Institute.
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