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A Genome-Wide Pharm...
A Genome-Wide Pharmacogenetic Study of Growth Hormone Responsiveness
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Dauber, A. (författare)
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Meng, Y. (författare)
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Audi, L. (författare)
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Vedantam, S. (författare)
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Weaver, B. (författare)
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Carrascosa, A. (författare)
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- Albertsson-Wikland, Kerstin, 1947 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Ranke, M. B. (författare)
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Jorge, A. A. L. (författare)
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Cara, J. (författare)
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Wajnrajch, M. P. (författare)
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Lindberg, A. (författare)
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Camacho-Hübner, C. (författare)
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Hirschhorn, J. N. (författare)
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(creator_code:org_t)
- 2020-07-11
- 2020
- Engelska.
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:10, s. 3203-3214
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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. © Endocrine Society 2020.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- genome-wide association
- growth hormone
- pharmacogenetics
- short stature
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Dauber, A.
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Meng, Y.
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Audi, L.
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Vedantam, S.
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Weaver, B.
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Carrascosa, A.
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visa fler...
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Albertsson-Wikla ...
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Ranke, M. B.
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Jorge, A. A. L.
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Cara, J.
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Wajnrajch, M. P.
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Lindberg, A.
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Camacho-Hübner, ...
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Hirschhorn, J. N ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
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Göteborgs universitet