Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height.

ABSTRACT: GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. To uncover 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, are enriched at height GWAS loci, particularly near differentially expressed growth plate genes, and enriched for binding motifs of transcription factors with roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at CHSY1, we identified a candidate causal variant (rs9920291) overlapping an open chromatin

SUBMITTER: Guo M 

PROVIDER: S-EPMC5716665 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature