Causal graphical models in systems genetics: A unified framework for joint inference of causal network and genetic architecture for correlated phenotypes

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. 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.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS288 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Causality, computing, and complexity

I discuss two categories of causal relationships: primitive causal interactions of the sort characterized by Phil Dowe and the more general manipulable causal relationships as defined by James Woodward. All primitive causal interactions are manipulable causal relationships, but there are manipulable causal relationships that are not primitive causal interactions. I’ll call the latter constructed causal relationships, and I’ll argue that constructed causal relationships serve as a foundation for both computing and complex systems. -/- Perhaps even more interesting are autonomous causal relationships. These are constructed causal relationships in which the causal mechanism resides primarily in the effect. A typical example is a software execution engine. Software execution engines are on the effect side of a cause-effect relationship in which software is the cause and the behavior of the execution engine is the effect. The mechanism responsible for that causal relationship resides in the execution engine

Detecting and quantifying causal associations in large nonlinear time series datasets

Identifying causal relationships and quantifying their strength from observational time series data are key problems in disciplines dealing with complex dynamical systems such as the Earth system or the human body. Data-driven causal inference in such systems is challenging since datasets are often high dimensional and nonlinear with limited sample sizes. Here, we introduce a novel method that flexibly combines linear or nonlinear conditional independence tests with a causal discovery algorithm to estimate causal networks from large-scale time series datasets. We validate the method on time series of well-understood physical mechanisms in the climate system and the human heart and using large-scale synthetic datasets mimicking the typical properties of real-world data. The experiments demonstrate that our method outperforms state-of-the-art techniques in detection power, which opens up entirely new possibilities to discover and quantify causal networks from time series across a range of research fields