We first focused on existing pathway and gene prioritization methods: (1) MAGENTA13, a method designed to identify gene sets enriched in GWAS data, and (2) GRAIL14, which uses published literature to highlight connections between likely relevant genes within GWAS loci. As expected, the GRAIL and MAGENTA analyses confirmed several previously identified gene sets and pathways clearly relevant to skeletal growth, but in the larger sample they also provided evidence for additional known and novel genes, gene sets and protein complexes not identified in our previous smaller study (for example, FGF signaling, WNT signaling, osteoglycin, and other genes related to bone or cartilage development) (Supplementary Tables 12–13 and Supplementary Fig. 7).
