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Genetic determinants of growth hormone and GH-related phenotypes

Hallengren, Erik LU ; Almgren, Peter LU ; Svensson, Malin LU ; Gallo, Widet LU orcid ; Engström, Gunnar LU ; Persson, Margaretha LU orcid and Melander, Olle LU orcid (2017) In BMC Genomics 18. p.1-9
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
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
in
BMC Genomics
volume
18
article number
822
pages
1 - 9
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85044064947
  • pmid:29065852
ISSN
1471-2164
DOI
10.1186/s12864-017-4219-z
language
English
LU publication?
yes
id
7313bc39-872f-4f89-a4de-62cefa1b8fba
date added to LUP
2019-06-24 09:37:17
date last changed
2024-03-13 11:08:47
@article{7313bc39-872f-4f89-a4de-62cefa1b8fba,
  abstract     = {{<p>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.</p><p>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).</p><p>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.</p>}},
  author       = {{Hallengren, Erik and Almgren, Peter and Svensson, Malin and Gallo, Widet and Engström, Gunnar and Persson, Margaretha and Melander, Olle}},
  issn         = {{1471-2164}},
  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}},
  language     = {{eng}},
  month        = {{10}},
  pages        = {{1--9}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Genomics}},
  title        = {{Genetic determinants of growth hormone and GH-related phenotypes}},
  url          = {{http://dx.doi.org/10.1186/s12864-017-4219-z}},
  doi          = {{10.1186/s12864-017-4219-z}},
  volume       = {{18}},
  year         = {{2017}},
}