Epigentic profiling of murine proximal and distal femoral growth plates at E15.5 of mouse gestation

GWAS have identified hundreds of loci associated with height.However, determining causal mechanisms is challenging, especially since height-relevant tissues such as the growth plate are difficult to study. To discover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology and are enriched at height GWAS loci, particularly near differentially expressed growth plate genes. These regions are also enriched in binding motifs of transcription factors with known roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at the CHYS1 locus, we identified a potentially causal variant overlapping an open chromatin region and predicted to alter binding of HOXD13, important for skeletal development. Thus, integrating biologically relevant epigenetic information (here, from mouse growth plate) with genetic association results can identify biological mechanisms important for human growth. Examination of open chromatin regions in two different growth plates (proximal vs distal femur) at E15.5