Figure 1. Workflow of the systems genetics approach for trans-eQTL identification.

The new systems genetics approach is based on four steps that are performed before the trans-eQTL analysis in order to efficiently reduce the number of analyzed genes: 1) Identification of the gene expression modules (M) that characterize CD4+ T cell gene expression 2) Enrichment analysis of a specific biological process that is related to the trait of interest 3) Construction of the functional-based networks using biological knowledge within the significantly enriched modules 4) Network analysis to identify those genes that are likely to play a central role in the functional-based networks 5) Trans-eQTL analysis using the subset of genes that show the highest centrality in each module. Abbreviations: AT, association transfer between organisms; BK, curated biological pathway knowledge; CP, computational predictions; G, gene; M, module; PI, physical interactions; TM, text-mining.