Supplementary Figure 10: Enrichment of trait-associated modules in curated gene sets from recent studies

. Enrichment of trait-associated modules in six curated gene sets from three recent studies. The first two gene sets were taken from Marouli et al.³² and correspond to genes comprising height-associated ExomeChip variants (n = 475 genes) and genes known to be involved in skeletal growth disorders (n = 266 genes), respectively. The third gene set was taken from de Lange et al.⁶¹ and corresponds to genes causing monogenic immunodeficiency disorders (n = 316 genes). Lastly, three gene sets relevant for type 2 diabetes (T2D) were taken from Fuchsberger et al.⁶² and correspond to genes in literature-curated pathways that are believed to be linked to T2D (we distinguished between genes in cytokine signalling pathways [n = 384 genes] and other pathways [n = 390 genes]) and genes causing monogenic diabetes (n = 81 genes). We then considered corresponding GWAS traits in our hold-out set, namely height, all immune-related disorders, and T2D. We tested all modules associated with these GWAS traits for enrichment in these six external gene sets. Enrichment was tested using the hypergeometric distribution and p-values were adjusted to control FDR using the Benjamini-Hochberg method. The heatmap shows for each GWAS (row) the fraction of trait-associated modules that significantly overlap with a given gene set (column). It can be seen that modules associated with a given trait predominantly overlap the external gene sets that are expected to be relevant for that trait. 61. de Lange, K. M. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat. Genet. 49, 256–261 (2017). 62. Fuchsberger, C. et al. The genetic architecture of type 2 diabetes. Nature 536, 41–47 (2016).