Dataset Information

A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness.

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 outcome measures

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.

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.

SUBMITTER: Dauber A

PROVIDER: S-EPMC7446971 | biostudies-literature |

REPOSITORIES: biostudies-literature

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