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

Henry Sung Ching Wong, Ying Ju Lin, Hsing Fang Lu, Wen Ling Liao, Chien Hsiun Chen, Jer Yuarn Wu, Wei Chiao Chang, Fuu Jen Tsai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number91
JournalJournal of Biomedical Science
Volume26
Issue number1
DOIs
Publication statusPublished - Nov 7 2019

Fingerprint

Drug Repositioning
Genes
Pharmaceutical Preparations
Endocrine System
Genetic Loci
Human Growth Hormone
Drug Discovery
Multigene Family
Computational Biology
Growth Hormone
Bioinformatics
Cytokines
Pipelines
Therapeutics

Keywords

  • Drug repositioning/repurposing
  • Familial short stature
  • Genome-wide association study
  • Pharmacogenomics
  • Single-nucleotide polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

Genomic interrogation of familial short stature contributes to the discovery of the pathophysiological mechanisms and pharmaceutical drug repositioning. / Wong, Henry Sung Ching; Lin, Ying Ju; Lu, Hsing Fang; Liao, Wen Ling; Chen, Chien Hsiun; Wu, Jer Yuarn; Chang, Wei Chiao; Tsai, Fuu Jen.

In: Journal of Biomedical Science, Vol. 26, No. 1, 91, 07.11.2019.

Research output: Contribution to journalArticle

Wong, Henry Sung Ching ; Lin, Ying Ju ; Lu, Hsing Fang ; Liao, Wen Ling ; Chen, Chien Hsiun ; Wu, Jer Yuarn ; Chang, Wei Chiao ; Tsai, Fuu Jen. / Genomic interrogation of familial short stature contributes to the discovery of the pathophysiological mechanisms and pharmaceutical drug repositioning. In: Journal of Biomedical Science. 2019 ; Vol. 26, No. 1.
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AU - Wu, Jer Yuarn

AU - Chang, Wei Chiao

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