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Olle Melander

Principal investigator

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Genetic determinants of growth hormone and GH-related phenotypes

Author

  • Erik Hallengren
  • Peter Almgren
  • Malin Svensson
  • Widet Gallo
  • Gunnar Engström
  • Margaretha Persson
  • Olle Melander

Summary, in English

BACKGROUND: Higher fasting Growth Hormone (GH) has been associated with increased cardiovascular morbidity and mortality. Our objective was to find genetic determinants of fasting GH in order to facilitate future efforts of analyzing the association between fasting growth hormone and cardiovascular disease. A genome-wide association study (GWAS) was performed in a discovery cohort of 4134 persons (58% females; age 46-68 yrs), linking SNPs to fasting hs-GH. Fifteen SNPs were replicated in an independent cohort of 5262 persons (28.9% females; age 56-85 yrs). The best performing SNP was analyzed vs GH-related variables in a third independent cohort (n = 24,047; 61% females; age 44-73 yrs). A candidate gene approach searched for significant SNPs in the genes GH1 and GHR in the discovery cohort and was replicated as previously described.

RESULTS: In the GWAS, the minor allele of rs7208736 was associated with lower GH in the discovery cohort (p = 5.15*10^-6) and the replication cohort (p = 0.005). The GH reducing allele was associated with lower BMI (P = 0.026) and waist (P = 0.021) in males only. In the candidate gene approach rs13153388 in the GHR-gene was associated with elevated GH-levels (P = 0.003) in the discovery cohort only and reduced height (P = 0.003).

CONCLUSION: In the first GWAS ever for GH, we identify a novel locus on chromosome 17 associated with fasting GH levels, suggesting novel biological mechanisms behind GH secretion and GH-related traits. The candidate gene approach identified a genetic variant in the GHR, which was associated with an elevation of fasting hs-GH and lower height suggesting reduced GHR ligand sensitivity. Our findings need further replication.

Department/s

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Applied Microbiology
  • Cardiovascular Research - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Internal Medicine - Epidemiology

Publishing year

2017-10-24

Language

English

Pages

1-9

Publication/Series

BMC Genomics

Volume

18

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Medical Genetics

Keywords

  • Aged
  • Body Weights and Measures
  • Comorbidity
  • Databases, Genetic
  • Female
  • Genetic Association Studies
  • Genetic Variation
  • Genetics, Population
  • Genome-Wide Association Study
  • Human Growth Hormone/blood
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sweden

Status

Published

Research group

  • Cardiovascular Research - Hypertension
  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1471-2164