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

doi:10.1186/s12929-019-0581-2

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 journal › Article › peer-review

1 Citation (Scopus)

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 language	English
Article number	91
Journal	Journal of Biomedical Science
Volume	26
Issue number	1
DOIs	https://doi.org/10.1186/s12929-019-0581-2
Publication status	Published - Nov 7 2019

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)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12929-019-0581-2

Cite this

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

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.",

keywords = "Drug repositioning/repurposing, Familial short stature, Genome-wide association study, Pharmacogenomics, Single-nucleotide polymorphism",

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

note = "Publisher Copyright: {\textcopyright} 2019 The Author(s).",

year = "2019",

month = nov,

day = "7",

doi = "10.1186/s12929-019-0581-2",

language = "English",

volume = "26",

journal = "Journal of Biomedical Science",

issn = "1021-7770",

publisher = "BioMed Central",

number = "1",

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TY - JOUR

T1 - Genomic interrogation of familial short stature contributes to the discovery of the pathophysiological mechanisms and pharmaceutical drug repositioning

AU - Wong, Henry Sung Ching

AU - Lin, Ying Ju

AU - Lu, Hsing Fang

AU - Liao, Wen Ling

AU - Chen, Chien Hsiun

AU - Wu, Jer Yuarn

AU - Chang, Wei Chiao

AU - Tsai, Fuu Jen

PY - 2019/11/7

Y1 - 2019/11/7

N2 - 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.

AB - 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.

KW - Drug repositioning/repurposing

KW - Familial short stature

KW - Genome-wide association study

KW - Pharmacogenomics

KW - Single-nucleotide polymorphism

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DO - 10.1186/s12929-019-0581-2

M3 - Article

C2 - 31699087

AN - SCOPUS:85074707209

SN - 1021-7770

VL - 26

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

IS - 1

M1 - 91

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

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MOESM5 of Genomic interrogation of familial short stature contributes to the discovery of the pathophysiological mechanisms and pharmaceutical drug repositioning

MOESM4 of Genomic interrogation of familial short stature contributes to the discovery of the pathophysiological mechanisms and pharmaceutical drug repositioning

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