Genomic interrogation of familial short stature contributes to the discovery of the pathophysiological mechanisms and pharmaceutical drug repositioning.

BACKGROUND

Genetic factors, dysregulation in the endocrine system, cytokine and paracrine factors are implicated in the pathogenesis of familial short stature (FSS). Nowadays, the treatment choice for FSS is limited, with only recombinant human growth hormone (rhGH) being available.

METHODS

Herein, starting from the identification of 122 genetic loci related to FSS, we adopted a genetic-driven drug discovery bioinformatics pipeline based on functional annotation to prioritize crucial biological FSS-related genes. These genes were suggested to be potential targets for therapeutics.

RESULTS

We discovered five druggable subnetworks, which contained seven FSS-related genes and 17 druggable targerts.

CONCLUSIONS

This study provides a valuable drug repositioning accompanied by corresponding targetable gene clusters for FSS therapy.