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. 2010 Mar 1;4(1):320-339.
doi: 10.1214/09-aoas288.

CAUSAL GRAPHICAL MODELS IN SYSTEMS GENETICS: A UNIFIED FRAMEWORK FOR JOINT INFERENCE OF CAUSAL NETWORK AND GENETIC ARCHITECTURE FOR CORRELATED PHENOTYPES (V体育安卓版)

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CAUSAL GRAPHICAL MODELS IN SYSTEMS GENETICS: A UNIFIED FRAMEWORK FOR JOINT INFERENCE OF CAUSAL NETWORK AND GENETIC ARCHITECTURE FOR CORRELATED PHENOTYPES

Elias Chaibub Neto et al. Ann Appl Stat. .

Abstract

Causal inference approaches in systems genetics exploit quantitative trait loci (QTL) genotypes to infer causal relationships among phenotypes. The genetic architecture of each phenotype may be complex, and poorly estimated genetic architectures may compromise the inference of causal relationships among phenotypes. Existing methods assume QTLs are known or inferred without regard to the phenotype network structure. In this paper we develop a QTL-driven phenotype network method (QTLnet) to jointly infer a causal phenotype network and associated genetic architecture for sets of correlated phenotypes VSports手机版. Randomization of alleles during meiosis and the unidirectional influence of genotype on phenotype allow the inference of QTLs causal to phenotypes. Causal relationships among phenotypes can be inferred using these QTL nodes, enabling us to distinguish among phenotype networks that would otherwise be distribution equivalent. We jointly model phenotypes and QTLs using homogeneous conditional Gaussian regression models, and we derive a graphical criterion for distribution equivalence. We validate the QTLnet approach in a simulation study. Finally, we illustrate with simulated data and a real example how QTLnet can be used to infer both direct and indirect effects of QTLs and phenotypes that co-map to a genomic region. .

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VSports手机版 - Figures

Fig. 1
Fig. 1
Example network with five phenotypes and four QTLs.
Fig. 2
Fig. 2
Output of a single trait QTL mapping analysis for the phenotypes in Figure 1. Dashed and pointed arrows represent direct and indirect QTL/phenotype causal relationships, respectively.
Fig. 3
Fig. 3
QTL mapping tailored to the network structure. (a) and (b) display the results of QTL mapping according to slightly altered network structures from Figure 1. Dashed, pointed and wiggled arrows represent, respectively, direct, indirect and incorrect QTL/phenotype causal relationships.
Fig. 4
Fig. 4
Model-averaged posterior network. Arrow darkness is proportional to the posterior probability of the causal relation computed via Bayesian model averaging. For each pair of phenotypes, the figure displays the causal relationship (presence or absence of an arrow) with highest posterior probability. Light grey nodes represent QTLs and show their chromosome number and position in centimorgans. Riken represents the riken gene 6530401C20Rik.

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