{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["105(10)"],"submitter":["Dauber A"],"funding":["Pfizer"],"pubmed_abstract":["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."],"journal":["The Journal of clinical endocrinology and metabolism"],"pagination":["dgaa443"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7446971"],"repository":["biostudies-literature"],"pubmed_title":["A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness."],"pmcid":["PMC7446971"],"pubmed_authors":["Weaver B","Lindberg A","Jorge AAL","Albertsson-Wikland K","Meng Y","Audi L","Wajnrajch MP","Vedantam S","Hirschhorn JN","Cara J","Ranke MB","Camacho-Hubner C","Dauber A","Carrascosa A"],"additional_accession":[]},"is_claimable":false,"name":"A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2024-11-13T00:48:01.661Z","creation":"2020-09-05T07:11:44Z"},"accession":"S-EPMC7446971","cross_references":{"pubmed":["32652002"],"doi":["10.1210/clinem/dgaa443"]}}