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Examining the causal association of fasting glucose with blood pressure in healthy children and adolescents: a Mendelian randomization study employing common genetic variants of fasting glucose.

Goharian, T S; Andersen, L B; Franks, Paul LU ; Wareham, N J; Brage, S; Veidebaum, T; Ekelund, Ulf LU ; Lawlor, D A; Loos, R J F and Grøntved, A (2015) In Journal of Human Hypertension 29(3). p.179-184
Abstract
The aim of the study was to determine whether genetically raised fasting glucose (FG) levels are associated with blood pressure (BP) in healthy children and adolescents. We used 11 common genetic variants of FG discovered in genome-wide association studies (GWAS), including the rs560887 single-nucleotide polymorphism (SNP) located in the G6PC2 locus found to be robustly associated with FG in children and adolescents, as an instrument to associate FG with resting BP in 1506 children and adolescents from the European Youth Heart Study (EYHS). Rs560887 was associated with increased FG levels corresponding to an increase of 0.08 mmol l(-1) (P=2.4 × 10(-8)). FG was associated with BP, independent of other important determinants of BP in... (More)
The aim of the study was to determine whether genetically raised fasting glucose (FG) levels are associated with blood pressure (BP) in healthy children and adolescents. We used 11 common genetic variants of FG discovered in genome-wide association studies (GWAS), including the rs560887 single-nucleotide polymorphism (SNP) located in the G6PC2 locus found to be robustly associated with FG in children and adolescents, as an instrument to associate FG with resting BP in 1506 children and adolescents from the European Youth Heart Study (EYHS). Rs560887 was associated with increased FG levels corresponding to an increase of 0.08 mmol l(-1) (P=2.4 × 10(-8)). FG was associated with BP, independent of other important determinants of BP in conventional multivariable analysis (systolic BP z-score: 0.32 s.d. per increase in mmol l(-1) (95% confidence interval (CI) 0.20-0.44, P=1.9 × 10(-7)), diastolic BP z-score: 0.13 s.d. per increase in mmol l(-1) (95% CI 0.04-0.21, P=3.2 × 10(-3)). This association was not supported by the Mendelian randomization approach, neither from instrumenting FG from all 11 variants nor from the rs560887, where non-significant associations of glucose with BP were observed. The results of this study could not support a causal association between FG and BP in healthy children and adolescents; however, it is possible that rs560887 has pleiotropic effects on unknown factors with a BP lowering effect or that these results were due to a lack of statistical power.Journal of Human Hypertension advance online publication, 31 July 2014; doi:10.1038/jhh.2014.63. (Less)
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Contribution to journal
publication status
published
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in
Journal of Human Hypertension
volume
29
issue
3
pages
179 - 184
publisher
Nature Publishing Group
external identifiers
  • pmid:25078492
  • wos:000349671500007
  • scopus:84926146007
ISSN
1476-5527
DOI
10.1038/jhh.2014.63
language
English
LU publication?
yes
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90e27df5-7bbf-4e10-81e6-864a86acacec (old id 4615934)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25078492?dopt=Abstract
date added to LUP
2014-09-02 18:47:05
date last changed
2017-01-01 03:17:36
@article{90e27df5-7bbf-4e10-81e6-864a86acacec,
  abstract     = {The aim of the study was to determine whether genetically raised fasting glucose (FG) levels are associated with blood pressure (BP) in healthy children and adolescents. We used 11 common genetic variants of FG discovered in genome-wide association studies (GWAS), including the rs560887 single-nucleotide polymorphism (SNP) located in the G6PC2 locus found to be robustly associated with FG in children and adolescents, as an instrument to associate FG with resting BP in 1506 children and adolescents from the European Youth Heart Study (EYHS). Rs560887 was associated with increased FG levels corresponding to an increase of 0.08 mmol l(-1) (P=2.4 × 10(-8)). FG was associated with BP, independent of other important determinants of BP in conventional multivariable analysis (systolic BP z-score: 0.32 s.d. per increase in mmol l(-1) (95% confidence interval (CI) 0.20-0.44, P=1.9 × 10(-7)), diastolic BP z-score: 0.13 s.d. per increase in mmol l(-1) (95% CI 0.04-0.21, P=3.2 × 10(-3)). This association was not supported by the Mendelian randomization approach, neither from instrumenting FG from all 11 variants nor from the rs560887, where non-significant associations of glucose with BP were observed. The results of this study could not support a causal association between FG and BP in healthy children and adolescents; however, it is possible that rs560887 has pleiotropic effects on unknown factors with a BP lowering effect or that these results were due to a lack of statistical power.Journal of Human Hypertension advance online publication, 31 July 2014; doi:10.1038/jhh.2014.63.},
  author       = {Goharian, T S and Andersen, L B and Franks, Paul and Wareham, N J and Brage, S and Veidebaum, T and Ekelund, Ulf and Lawlor, D A and Loos, R J F and Grøntved, A},
  issn         = {1476-5527},
  language     = {eng},
  number       = {3},
  pages        = {179--184},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Human Hypertension},
  title        = {Examining the causal association of fasting glucose with blood pressure in healthy children and adolescents: a Mendelian randomization study employing common genetic variants of fasting glucose.},
  url          = {http://dx.doi.org/10.1038/jhh.2014.63},
  volume       = {29},
  year         = {2015},
}