Figure 3.

A subnetwork of apolipoprotein genes is significantly enriched for mutations in European, East Asian, and Native Hawaiian ancestries associated with triglyceride levels

The largest significantly altered subnetwork (p value $<$ 0.05) for triglyceride levels contains overlapping gene subnetworks for each of the European, East Asian, and Native Hawaiian ancestries when analyzed independently with Hierarchical HotNet.¹⁶ Each node in the network represents a gene. The shading of each node indicates the statistical significance of the association of that gene with triglyceride levels in a particular cohort. Two genes are connected if their protein products interact based on the ReactomeFI 2016⁴⁸ (European, East Asian) or iRefIndex 15.0⁴⁹ (Native Hawaiian) protein-protein interaction networks. Several genes from the apolipoprotein gene family are significantly associated with triglyceride levels in both the European and East Asian cohorts (see data and code availability). Additionally, the interactions between them form a highly connected subnetwork. Smaller subnetworks identified in the Native Hawaiian cohort are distal modules that are connected to the subnetwork detected in the European cohort. Not all genes in the largest significantly altered subnetwork for the Native Hawaiian ancestry group are shown for visualization purposes (127 not pictured here). Genes that contain SNPs previously associated to triglyceride levels in a European cohort in the GWAS Catalog are indicated with †. Similarly, genes that contain SNPs previously associated with triglyceride levels in a non-European cohort in the GWAS Catalog are indicated with ‡. The studies identifying these associations are given in Table S25.