DEPICT also prioritizes genes that are new candidates for playing a role in skeletal growth. The genes newly and strongly implicated in this study included not only genes with obvious relationships to skeletal biology, such as SOX5 and collagen genes, but also genes that have no clear published connection to skeletal growth, and likely represent as yet unknown biology (Table 3 and Supplementary Table 16). DEPICT strongly prioritized genes that do not have published annotations related to growth-related pathways but are predicted to be in gene sets that are both enriched in the associated loci and clearly connected to growth. These include genes newly predicted to be in pathways related to cartilage or bone development (FAM101A, CRISPLD1 and the noncoding RNA LINC00476), collagen or extracellular matrix (GLT8D2, CCDC3, and ZCCHC24), histone demethylation (ATAD2B and TSTD2) and other genes predicted to have skeletal phenotypes but not currently annotated as belonging to relevant pathways (ARSJ, PSKH1, COPZ2, ADAMTS17 and the microRNA cluster MIR17HG). Of note, mutations in both ADAMTS17 and MIR17HG have been identified as causes of syndromic short stature in humans15,16.
