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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

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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.

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Acknowledgements

This study obtained funding from the following sources: The Danish Heart Foundation, The Danish Medical Research Council Health Foundation, The Danish Council for Sports Research, The Foundation in Memory of Asta Florida Bolding Renée Andersen, The Faculty of Health Sciences, University of Southern Denmark, The Danish Independent Research Council, The Estonian Research Council (SF094000s12) and The UK Medical Research Council. NJW, UE, SB and RJFL work in a UK Medical Research Council funded unit and DAL works in a Centre that receives funds from the UK Medical Research Council (G0600705) and University of Bristol. The views expressed in this paper are those of the authors and not necessarily any funding body. None of the funding bodies influenced data collection, analysis or interpretation of results.

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Correspondence to A Grøntved.

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Supplementary Information accompanies this paper on the Journal of Human Hypertension website

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Goharian, T., Andersen, L., Franks, P. et al. 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. J Hum Hypertens 29, 179–184 (2015). https://doi.org/10.1038/jhh.2014.63

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