scholarly journals 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

2014 ◽  
Vol 29 (3) ◽  
pp. 179-184 ◽  
Author(s):  
T S Goharian ◽  
L B Andersen ◽  
P W Franks ◽  
N J Wareham ◽  
S Brage ◽  
...  
2019 ◽  
Vol 178 (7) ◽  
pp. 1069-1074 ◽  
Author(s):  
Luis E. Simental-Mendía ◽  
Gabriela Hernández-Ronquillo ◽  
Claudia I. Gamboa-Gómez ◽  
Rita Gómez-Díaz ◽  
Martha Rodríguez-Morán ◽  
...  

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Doretta Caramaschi ◽  
Charlie Hatcher ◽  
Rosa H. Mulder ◽  
Janine F. Felix ◽  
Charlotte A. M. Cecil ◽  
...  

AbstractThe occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study, we analyzed the association of genome-wide blood DNA methylation with the occurrence of seizures in ~ 800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood, and adolescence (peripheral blood). We also analyzed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e., using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1–5% absolute methylation difference at pFDR < 0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In conclusion, we show a suggestive link between seizures and blood DNA methylation while at the same time exploring the limitations of conducting such study.


2013 ◽  
Vol 26 (5) ◽  
pp. 643-656 ◽  
Author(s):  
M. D. Defago ◽  
D. Gu ◽  
J. E. Hixson ◽  
L. C. Shimmin ◽  
T. K. Rice ◽  
...  

Diabetologia ◽  
2011 ◽  
Vol 55 (2) ◽  
pp. 331-339 ◽  
Author(s):  
G. A. Walford ◽  
T. Green ◽  
B. Neale ◽  
T. Isakova ◽  
J. I. Rotter ◽  
...  

2010 ◽  
Vol 109 (4) ◽  
pp. 1125-1132 ◽  
Author(s):  
Niels C. Møller ◽  
Anders Grøntved ◽  
Niels Wedderkopp ◽  
Mathias Ried-Larsen ◽  
Peter L. Kristensen ◽  
...  

Raised blood pressure (BP) response during exercise independently predicts future hypertension. Subjects with higher BP in childhood also have elevated BP later in life. Therefore, the factors related to the regulation of exercise BP in children needs to be well understood. We hypothesized that physiological cardiovascular disease (CVD) risk factors would influence BP response during exercise in children and adolescents. This is a cross-sectional study of 439 Danish third-grade children and 364 ninth-grade adolescents. Systolic blood pressure (SBP) was measured with sphygmomanometer during a maximal aerobic fitness test. Examined CVD risk factors were high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol, triglyceride, homeostasis model of assessment of insulin resistance (HOMA-IR) score, body mass index (BMI), waist circumference, and aerobic fitness. A random effect model was used to test the hypotheses. In boys, HOMA-IR score and BMI were positively related to SBP response during exercise (β = 1.03, P = 0.001, and β = 0.58, P = 0.017, respectively). The effects sizes of HOMA-IR score and BMI and the significance levels only changed slightly (β = 0.91, P = 0.004, and β = 0.43, P = 0.08, respectively) when the two variables were added in the same model. A significant positive association was observed between aerobic fitness and SBP response in girls (β = 3.13 and P = 0.002). HOMA-IR score and BMI were found to be positively related to the SBP response in male children and youth. At least partly, adiposity and insulin sensitivity seem to influence exercise SBP through different mechanisms. The positive relationship observed between aerobic fitness and SBP response in girls remains unexplainable for us, although post hoc analyses revealed that it was the case in the ninth graders only.


2012 ◽  
Vol 166 (2) ◽  
pp. 301-306 ◽  
Author(s):  
Celia Aradillas-García ◽  
Martha Rodríguez-Morán ◽  
María Eugenia Garay-Sevilla ◽  
Juan Manuel Malacara ◽  
Ramón Alberto Rascon-Pacheco ◽  
...  

ObjectiveSeveral cutoff points of the homeostasis model assessment of insulin resistance (HOMA-IR; varying from 2.5 to 4.0) have been suggested for diagnosing IR in youth. In this study, we determined the distribution of the HOMA-IR in Mexican children and adolescents.Design and methodsA total of 6132 children and adolescents from San Luis Potosi, León, Queretaro, and Durango, which are cities in central and northern Mexico, were enrolled in a population-based cross-sectional study. Eligible participants were apparently healthy children and adolescents aged 6–18 years. Pregnancy and the presence of chronic illnesses were exclusion criteria.ResultsA total of 3701 (60.3%) girls and 2431 (39.7%) boys were included in this study. In the overall population, the mean body mass index, insulin levels, and fasting glucose levels were 21.8±1.3 kg/m2, 7.1±3.2 μU/ml, and 86.2±10.0 mg/dl respectively. The concentrations of insulin and fasting glucose gradually increased from 6 to 12 years of age, whereas the concentrations tended to plateau in the 13- to 18-year-old population. The absolute mean of the HOMA-IR was 2.89±0.7. The HOMA-IR gradually increased with age and reached a plateau at 13 years of age.ConclusionsBecause the insulin concentrations, glucose levels, and HOMA-IR exhibited a gradual increase with age that was not related to obesity, our results suggested that the evaluation of IR in children should be based on percentiles of the HOMA-IR rather than a dichotomous value derived from a single cutoff point.


2019 ◽  
Author(s):  
Doretta Caramaschi ◽  
Charlie Hatcher ◽  
Rosa H. Mulder ◽  
Janine F. Felix ◽  
Charlotte A. M. Cecil ◽  
...  

ABSTRACTThe occurrence of seizures in childhood is often associated with neurodevelopmental impairments and school underachievement. Common genetic variants associated with epilepsy have been identified and epigenetic mechanisms have also been suggested to play a role. In this study we analysed the association of genome-wide blood DNA methylation with the occurrence of seizures in ∼800 children from the Avon Longitudinal Study of Parents and Children, UK, at birth (cord blood), during childhood and adolescence (peripheral blood). We also analysed the association between the lifetime occurrence of any seizures before age 13 with blood DNA methylation levels. We sought replication of the findings in the Generation R Study and explored causality using Mendelian randomization, i.e. using genetic variants as proxies. The results showed five CpG sites which were associated cross-sectionally with seizures either in childhood or adolescence (1-5% absolute methylation difference at pFDR<0.05), although the evidence of replication in an independent study was weak. One of these sites was located in the BDNF gene, which is highly expressed in the brain, and showed high correspondence with brain methylation levels. The Mendelian randomization analyses suggested that seizures might be causal for changes in methylation rather than vice-versa. In addition, seizure-associated methylation changes could affect other outcomes such as growth, cognitive skills and educational attainment. In conclusion, we present a link between seizures and DNA methylation which suggests that DNA methylation changes might mediate some of the effects of seizures on growth and neurodevelopment.


2013 ◽  
Vol 94 (6) ◽  
pp. 798-803 ◽  
Author(s):  
Z R Khabibrakhmanova ◽  
T P Makarova ◽  
D I Sadykova

Aim. To study the specifics of lead, zinc, copper, magnesium and calcium metabolism in children and adolescents with essential arterial hypertension living in different ecological settings. Methods. 100 children and adolescents aged 13-17 years with arterial hypertension, living in «industrial» (52 patients) and «residential» (48 patients) areas were examined in cardiology ward. 33 healthy children and adolescents comparable by age and gender were included as healthy controls. According to 24-hour blood pressure monitoring, groups with stable, labile arterial hypertension and «white coat hypertension» were formed. The levels of elements in 24-hour urine and in serum were measured by atomic absorption spectrophotometry. Results. In children and adolescents with stable arterial hypertension living in industrial areas, parameters of 24-hour blood pressure monitoring (mean 24-hour and mean daytime systolic blood pressure values, time of systolic hypertension, mean 24-hour and mean daytime blood pressure values) were higher compared to the same parameters in children from residential areas, the difference was statistically significant. The study of elements metabolism revealed increased lead exposure in children with essential arterial hypertension living in industrial areas, and misbalance of essential elements in those patients compared to the same parameters in children from residential areas. Conclusion. Results suggest increased exposure to arterial hypertension and marked misbalance of essential elements in children and adolescents with essential arterial hypertension living in industrial areas.


2020 ◽  
Vol 41 (35) ◽  
pp. 3314-3322 ◽  
Author(s):  
Marina Cecelja ◽  
Louise Keehn ◽  
Li Ye ◽  
Tim D Spector ◽  
Alun D Hughes ◽  
...  

Abstract Aims Haemodynamic determinants of blood pressure (BP) include cardiac output (CO), systemic vascular resistance (SVR), and arterial stiffness. We investigated the heritability of these phenotypes, their association with BP-related single-nucleotide polymorphisms (SNPs), and the causal association between BP and arterial stiffness. Methods and results We assessed BP, central BP components, and haemodynamic properties (during a single visit) including CO, SVR, and pulse wave velocity (PWV, measure of arterial stiffness) in 3531 (1934 monozygotic, 1586 dizygotic) female TwinsUK participants. Heritability was estimated using structural equation modelling. Association with 984 BP-associated SNP was examined using least absolute shrinkage and selection operator (LASSO) and generalized estimating equation regression. One and two-sample Mendelian randomization (MR) was used to estimate the causal direction between BP and arterial stiffness including data on 436 419 UK Biobank participants. We found high heritability for systolic and pulsatile components of BP (&gt;50%) and PWV (65%) with overlapping genes accounting for &gt;50% of their observed correlation. Environmental factors explained most of the variability of CO and SVR (&gt;80%). Regression identified SNPs (n = 5) known to be associated with BP to also be associated with PWV. One-sample MR showed evidence of bi-directional causal association between BP and PWV in TwinsUK participants. Two-sample MR, confirmed a bi-directional causal effect of PWV on BP (inverse variance weighted (IVW) beta = 0.11, P &lt; 0.02) and BP on arterial stiffness (IVW beta = 0.004, P &lt; 0.0001). Conclusion The genetic basis of BP is mediated not only by genes regulating BP but also by genes that influence arterial stiffness. Mendelian randomization indicates a bi-directional causal association between BP and arterial stiffness.


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