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A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness Dauber, Andrew Meng, Yan Audí, Laura Vedantam, Sailaja Weaver, Benjamin Carrascosa Lezcano, Antonio Albertsson-Wikland, Kerstin Ranke, Michael B. Jorge, Alexander A. L. Cara, Jose Wajnrajch, Michael P. Lindberg, Anders Camacho-Hübner, Cecilia Hirschhorn, Joel N. Universitat Autònoma de Barcelona Growth hormone Pharmacogenetics Short stature Genome-wide association 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. 2020 Article https://ddd.uab.cat/record/238786 urn:10.1210/clinem/dgaa443 urn:oai:ddd.uab.cat:238786 urn:pmcid:PMC7446971 urn:pmc-uid:7446971 urn:pmid:32652002 urn:articleid:19457197v105p3203 urn:oai:pubmedcentral.nih.gov:7446971 http://hdl.handle.net/2072/455705 eng The journal of clinical endocrinology & metabolism ; Vol. 105 (july 2020), p. 3203-3214 open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/ application/pdf