%0 Journal Article
%T A graphical model approach for inferring large-scale networks integrating gene expression and genetic polymorphism
%A Jen-hwa Chu
%A Scott T Weiss
%A Vincent J Carey
%A Benjamin A Raby
%J BMC Systems Biology
%D 2009
%I BioMed Central
%R 10.1186/1752-0509-3-55
%X Here we describe a multistep approach to infer a gene-SNP network from gene expression and genotyped SNP data. Our approach is based on 1) construction of a graphical Gaussian model (GGM) based on small sample estimation of partial correlation and false-discovery rate multiple testing; 2) extraction of a subnetwork of genes directly linked to a target candidate gene of interest; 3) identification of cis-acting regulatory variants for the genes composing the subnetwork; and 4) evaluating the identified cis-acting variants for trans-acting regulatory effects of the target candidate gene. This approach identifies significant gene-gene and gene-SNP associations not solely on the basis of gene co-expression but rather through whole-network modeling. We demonstrate the method by building two complex gene-SNP networks around Interferon Receptor 12B2 (IL12RB2) and Interleukin 1B (IL1B), two biologic candidates in asthma pathogenesis, using 534,290 genotyped variants and gene expression data on 22,177 genes from total RNA derived from peripheral blood CD4+ lymphocytes from 154 asthmatics.Our results suggest that graphical models based on integrative genomic data are computationally efficient, work well with small samples, and can describe complex interactions among genes and polymorphisms that could not be identified by pair-wise association testing.Jansen and Nap [1] proposed expression quantitative trait locus (eQTL) mapping by considering gene transcript abundances as quantitative phenotypes. Identified eQTLs could then be tested as potential disease-susceptibility candidates in genetic association studies, with the expectation that variants with functional influence on gene expression would have a higher likelihood of influencing clinical traits. Initial studies examining the feasibility of such integrative genomic strategies in a variety of model organisms and in human populations have demonstrated that a substantial proportion of transcripts exhibit heritable expressio
%U http://www.biomedcentral.com/1752-0509/3/55