title: Using gene expression data to identify causal pathways between genotype and phenotype in a complex disease: application to Genetic Analysis Workshop 19.
abstract: We explore causal relationships between genotype, gene expression and phenotype in the Genetic Analysis Workshop 19 data. We compare the use of structural equation modeling and a Bayesian unified framework approach to infer the most likely causal models that gave rise to the data. Testing an exhaustive set of causal relationships between each single-nucleotide polymorphism, gene expression probe, and phenotype would be computationally infeasible, thus a filtering step is required. In addition to filtering based on pairwise associations, we consider weighted gene correlation network analysis as a method of clustering genes with similar function into a small number of modules. These modules capture the key functional mechanisms of genes while greatly reducing the number of relationships to test for in causal modeling.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ UK.
authors.forename: Holly F
authors.initials: HF
authors.lastname: Ainsworth
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ UK.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Cordell