A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness.
J Clin Endocrinol Metab
; 105(10)2020 10 01.
Article
en En
| MEDLINE
| ID: mdl-32652002
ABSTRACT
CONTEXT Individual patients vary in their response to growth hormone (GH). No large-scale genome-wide studies have looked for genetic predictors of GH responsiveness. OBJECTIVE:
To identify genetic variants associated with GH responsiveness.DESIGN:
Genome-wide association study (GWAS).SETTING:
Cohorts from multiple academic centers and a clinical trial. PATIENTS 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. INTERVENTION Association of more than 2 million variants was tested. MAIN OUTCOMEMEASURES:
Primaryanalysis:
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.RESULTS:
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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estatura
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Hormona de Crecimiento Humana
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Enanismo Hipofisario
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Sitios Genéticos
Tipo de estudio:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Child
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2020
Tipo del documento:
Article