Supplementary Figure 13: Modules Associated with IgA Nephropathy.

The top ten enriched GO biological processes, Reactome pathways and mouse mutant phenotypes are shown for two IgA nephropathy (IgAN) associated modules. P-values were computed using the non-central hypergeometric distribution (Methods). (a) IgAN-associated module identified using the consensus analysis in the InWeb protein-protein interaction network (n = 19 genes). The module comprises immune-related NF-κB signaling pathways. Enriched mouse mutant phenotypes for module gene homologs include perturbed immunoglobulin levels (IgM and IgG1). The module implicates in particular the NF-κB subunit REL as a candidate gene. The REL locus does not reach genome-wide significance in current GWASs for IgAN but is known to be associated with other immune disorders such as rheumatoid arthritis. (b) IgAN-associated module identified by the best-performing method (K1) in the InWeb protein-protein interaction network (n = 12 genes). Besides finding complement factors that are known to play a role in the disease (CFB and C4A), the module implicates novel candidate genes such as the chemokine Platelet Factor 4 Variant 1 (PF4V1) from a sub-threshold locus, and is enriched for coagulation cascade, a process known to be involved in kidney disease⁶². The top two enriched mouse mutant phenotypes are precisely “abnormal blood coagulation” and “glomerulonephritis”. 62. Madhusudhan, T., Kerlin, B. A. & Isermann, B. The emerging role of coagulation proteases in kidney disease. Nat. Rev. Nephrol. 12, 94–109 (2016).