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Fig. 4 | Genome Medicine

Fig. 4

From: Developing a network view of type 2 diabetes risk pathways through integration of genetic, genomic and functional data

Fig. 4

GWAS signal enrichment in an islet-specific network derived from T2D GWAS subsets. We built APCST networks filtered for islet RNA expression for each of the subsets of T2D GWAS loci defined by shared mechanistic mediation (refs [48, 49]). Number of seed genes for each of the subsets is displayed below the name of the phenotype. Enrichment in GWAS signals for linking nodes only was tested using a permutation scheme. Each dot in the figure depicts the −log10 p value of enrichment for association signals in a particular GWAS analysis. The results for T2D GWAS enrichment for the APCST networks built around the different T2D GWAS subsets are also represented (large red dots). The dotted red line represents nominal significance (p = 0.05) calculated as the empirical estimate of the null distribution from which the p value has been drawn. The strongest enrichment for T2D GWAS data in islet-filtered PPI data is observed for subsets of loci acting through reduced insulin secretion. The central network depicts the intersection of the seven networks created from the seven T2D GWAS locus subset categories. Nodes are coloured according to their PCS with grey nodes representing linking nodes. For the other networks, we have only named the nodes that are exclusive to each of the seven T2D GWAS locus subset category networks to ease interpretation. These networks are available in cytoscape and edge list format at [https://github.com/jfertaj/T2D_data_integration]

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