A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness.
Body Height
/ drug effects
Child
Cohort Studies
Dwarfism, Pituitary
/ drug therapy
Female
Galactosyltransferases
/ genetics
Genetic Loci
Genome-Wide Association Study
Human Growth Hormone
/ therapeutic use
Humans
Infant, Small for Gestational Age
Male
Molecular Chaperones
/ genetics
Pharmacogenomic Testing
/ statistics & numerical data
Polymorphism, Single Nucleotide
Sialyltransferases
/ genetics
Treatment Outcome
genome-wide association
growth hormone
pharmacogenetics
short stature
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
01 10 2020
01 10 2020
Historique:
received:
20
03
2020
accepted:
09
07
2020
pubmed:
12
7
2020
medline:
20
2
2021
entrez:
12
7
2020
Statut:
ppublish
Résumé
Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. To identify genetic variants associated with GH responsiveness. Genome-wide association study (GWAS). Cohorts from multiple academic centers and a clinical trial. A total of 614 individuals from 5 short stature cohorts receiving GH: 297 with idiopathic short stature, 276 with isolated GH deficiency, and 65 born small for gestational age. Association of more than 2 million variants was tested. Primary analysis: individual single nucleotide polymorphism (SNP) association with first-year change in height standard deviation scores. Secondary analyses: SNP associations in clinical subgroups adjusted for clinical variables; association of polygenic score calculated from 697 genome-wide significant height SNPs with GH responsiveness. No common variant associations reached genome-wide significance in the primary analysis. The strongest suggestive signals were found near the B4GALT4 and TBCE genes. After meta-analysis including replication data, signals at several loci reached or retained genome-wide significance in secondary analyses, including variants near ST3GAL6. There was no significant association with variants previously reported to be associated with GH response nor with a polygenic predicted height score. We performed the largest GWAS of GH responsiveness to date. We identified 2 loci with a suggestive effect on GH responsiveness in our primary analysis and several genome-wide significant associations in secondary analyses that require further replication. Our results are consistent with a polygenic component to GH responsiveness, likely distinct from the genetic regulators of adult height.
Identifiants
pubmed: 32652002
pii: 5870346
doi: 10.1210/clinem/dgaa443
pmc: PMC7446971
pii:
doi:
Substances chimiques
Molecular Chaperones
0
TBCE protein, human
0
Human Growth Hormone
12629-01-5
Galactosyltransferases
EC 2.4.1.-
Sialyltransferases
EC 2.4.99.-
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© Endocrine Society 2020.
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