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Searching for phenotypic causal networks involving complex traits: an application to European quail

Bruno D Valente12*, Guilherme JM Rosa23, Martinho A Silva1, Rafael B Teixeira4 and Robledo A Torres4

Author Affiliations

1 Department of Animal Sciences, Federal University of Minas Gerais, 30123-970, Brazil

2 Department of Animal Sciences, University of Wisconsin, Madison, Wisconsin USA

3 Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin USA

4 Department of Animal Sciences, Federal University of Viçosa, 36570-000, Brazil

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Genetics Selection Evolution 2011, 43:37  doi:10.1186/1297-9686-43-37

Published: 2 November 2011

Abstract

Background

Structural equation models (SEM) are used to model multiple traits and the casual links among them. The number of different causal structures that can be used to fit a SEM is typically very large, even when only a few traits are studied. In recent applications of SEM in quantitative genetics mixed model settings, causal structures were pre-selected based on prior beliefs alone. Alternatively, there are algorithms that search for structures that are compatible with the joint distribution of the data. However, such a search cannot be performed directly on the joint distribution of the phenotypes since causal relationships are possibly masked by genetic covariances. In this context, the application of the Inductive Causation (IC) algorithm to the joint distribution of phenotypes conditional to unobservable genetic effects has been proposed.

Methods

Here, we applied this approach to five traits in European quail: birth weight (BW), weight at 35 days of age (W35), age at first egg (AFE), average egg weight from 77 to 110 days of age (AEW), and number of eggs laid in the same period (NE). We have focused the discussion on the challenges and difficulties resulting from applying this method to field data. Statistical decisions regarding partial correlations were based on different Highest Posterior Density (HPD) interval contents and models based on the selected causal structures were compared using the Deviance Information Criterion (DIC). In addition, we used temporal information to perform additional edge orienting, overriding the algorithm output when necessary.

Results

As a result, the final causal structure consisted of two separated substructures: BW→AEW and W35→AFE→NE, where an arrow represents a direct effect. Comparison between a SEM with the selected structure and a Multiple Trait Animal Model using DIC indicated that the SEM is more plausible.

Conclusions

Coupling prior knowledge with the output provided by the IC algorithm allowed further learning regarding phenotypic causal structures when compared to standard mixed effects SEM applications.