scholarly journals Metabolomics: population epidemiology and concordance in Australian children aged 11–12 years and their parents

BMJ Open ◽  
2019 ◽  
Vol 9 (Suppl 3) ◽  
pp. 106-117 ◽  
Author(s):  
Susan Ellul ◽  
Melissa Wake ◽  
Susan A Clifford ◽  
Katherine Lange ◽  
Peter Würtz ◽  
...  

ObjectivesNuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a sample of Australian 11–12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent–child dyads.DesignThe population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children.SettingBlood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015–March 2016.Participants1180 children and 1325 parents provided a blood sample and had metabolomics data available. This included 1133 parent–child dyads (518 mother–daughter, 469 mother–son, 68 father–daughter and 78 father–son).Outcome measures228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis.ResultsWe identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent–child comparisons.ConclusionsWe describe the serum metabolite profiles from mid-childhood and adulthood in a population-based sample, together with a parent–child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ban-Hock Khor ◽  
◽  
Sharmela Sahathevan ◽  
Ayesha Sualeheen ◽  
Mohammad Syafiq Md Ali ◽  
...  

AbstractThe metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r =  − 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r =  − 0.197) and serum albumin (r =  − 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r =  − 0.168) and interleukin-6 concentrations (r =  − 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r =  − 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.


2019 ◽  
Vol 48 (3) ◽  
pp. 978-993 ◽  
Author(s):  
Tuulia Tynkkynen ◽  
Qin Wang ◽  
Jussi Ekholm ◽  
Olga Anufrieva ◽  
Pauli Ohukainen ◽  
...  

Abstract Background Quantitative molecular data from urine are rare in epidemiology and genetics. NMR spectroscopy could provide these data in high throughput, and it has already been applied in epidemiological settings to analyse urine samples. However, quantitative protocols for large-scale applications are not available. Methods We describe in detail how to prepare urine samples and perform NMR experiments to obtain quantitative metabolic information. Semi-automated quantitative line shape fitting analyses were set up for 43 metabolites and applied to data from various analytical test samples and from 1004 individuals from a population-based epidemiological cohort. Novel analyses on how urine metabolites associate with quantitative serum NMR metabolomics data (61 metabolic measures; n = 995) were performed. In addition, confirmatory genome-wide analyses of urine metabolites were conducted (n = 578). The fully automated quantitative regression-based spectral analysis is demonstrated for creatinine and glucose (n = 4548). Results Intra-assay metabolite variations were mostly <5%, indicating high robustness and accuracy of urine NMR spectroscopy methodology per se. Intra-individual metabolite variations were large, ranging from 6% to 194%. However, population-based inter-individual metabolite variations were even larger (from 14% to 1655%), providing a sound base for epidemiological applications. Metabolic associations between urine and serum were found to be clearly weaker than those within serum and within urine, indicating that urinary metabolomics data provide independent metabolic information. Two previous genome-wide hits for formate and 2-hydroxyisobutyrate were replicated at genome-wide significance. Conclusion Quantitative urine metabolomics data suggest broad novelty for systems epidemiology. A roadmap for an open access methodology is provided.


BMJ Open ◽  
2019 ◽  
Vol 9 (Suppl 3) ◽  
pp. 44-52 ◽  
Author(s):  
Julian Dascalu ◽  
Mengjiao Liu ◽  
Kate Lycett ◽  
Anneke C Grobler ◽  
Mingguang He ◽  
...  

ObjectivesTo describe distributions and concordance of retinal microvasculature measurements in a population-based sample of Australian parent–child dyads at child age 11–12 years.DesignCross-sectional Child Health CheckPoint study, between waves 6 and 7 of the national population-based Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven Australian cities, February 2015–March 2016.ParticipantsOf the 1874 participating families, 1288 children (51% girls) and 1264 parents (87% mothers, mean age 43.7) were analysed. Diabetic participants and non-biological pairs were excluded from concordance analyses.Outcome measuresRetinal photographs were taken by non-mydriatic fundus camera. Trained graders scored vascular calibre using semi-automated software, yielding estimates of central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) and arteriolar–venular ratio (AVR). Pearson’s correlation coefficients and multivariable linear regression models assessed parent–child concordance. Survey weights and methods accounted for LSAC’s complex sampling, stratification and clustering within postcodes.ResultsMean (SD) of CRAE and CRVE were larger in children (159.5 (11.8) and 231.1 (16.5) μm, respectively) than parents (151.5 (14.0) and 220.6 (19.0) μm), yielding similar AVR (children 0.69 (0.05), parents 0.69 (0.06)). Correlation coefficients for parent–child pairs were 0.22 (95% CI 0.16 to 0.27) for CRAE, 0.23 (95% CI 0.17 to 0.28) for CRVE and 0.18 (95% CI 0.13 to 0.24) for AVR. Mother–child and father–child values were similar (0.20 and 0.32 for CRAE, 0.22 and 0.29 for CRVE, respectively). Relationships attenuated slightly on adjustment for age, sex, blood pressure, diabetes and body mass index. Percentiles and concordance are presented for the whole sample and by sex.ConclusionsArteriolar and venular calibre were similar to previously documented measures in midlife adult and late childhood populations. Population parent–child concordance values align with moderate polygenic heritability reported in smaller studies.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260464
Author(s):  
Mikk Jürisson ◽  
Heti Pisarev ◽  
Anneli Uusküla ◽  
Katrin Lang ◽  
Marje Oona ◽  
...  

Background Multimorbidity is associated with physical-mental health comorbidity (PMHC). However, the scope of overlap between physical and mental conditions, associated factors, as well as types of mental illness involved are not well described in Eastern Europe. This study aims to assess the PMHC burden in the Estonian population. Methods In this population-based cross-sectional study we obtained health claims data for 55 chronic conditions from the Estonian Health Insurance Fund (EHIF) database, which captures data for all publicly insured individuals (n = 1 240 927 or 94.1% of the total population as of 31 December 2017). We assessed the period-prevalence (3 years) of chronic physical and mental health disorders, as well as associations between them, by age and sex. Results Half of the individuals (49.1% (95% CI 49.0–49.3)) had one or more chronic conditions. Mental health disorders (MHD) were present in 8.1% (8.1–8.2) of individuals, being higher among older age groups, women, and individuals with a higher number of physical conditions. PMHC was present in 6.2% (6.1–6.2) of the study population, and 13.1% (13.0–13.2) of the subjects with any chronic physical disorder also presented with at least one MHD. Dominating MHDs among PMHC patients were anxiety and depression. The prevalence of MHD was positively correlated with the number of physical disorders. We observed variation in the type of MHD as the number of physical comorbidities increased. The prevalence of anxiety, depression, and mental and behavioral disorders due to the misuse of alcohol and other psychoactive substances increased as physical comorbidities increased, but the prevalence of schizophrenia and dementia decreased with each additional physical disease. After adjusting for age and sex, this negative association changed the sign to a positive association in the case of dementia and mental and behavioral disorders due to psychoactive substance misuse. Conclusions The burden of physical-mental comorbidity in the Estonian population is relatively high. Further research is required to identify clusters of overlapping physical and mental disorders as well as the interactions between these conditions. Public health interventions may include structural changes to health care delivery, such as an increased emphasis on integrated care models that reduce barriers to mental health care.


Endocrinology ◽  
2017 ◽  
Vol 159 (1) ◽  
pp. 368-387 ◽  
Author(s):  
Pilar Argente-Arizón ◽  
Francisca Díaz ◽  
Purificación Ros ◽  
Vicente Barrios ◽  
Manuel Tena-Sempere ◽  
...  

Abstract Astrocytes participate in both physiological and pathophysiological responses to metabolic and nutrient signals. Although most studies have focused on the astrocytic response to weight gain due to high-fat/high-carbohydrate intake, surplus intake of a balanced diet also induces excess weight gain. We have accessed the effects of neonatal overnutrition, which has both age- and sex-dependent effects on weight gain, on hypothalamic inflammation/gliosis. Although both male and female Wistar rats accumulate excessive fat mass as early as postnatal day (PND) 10 with neonatal overnutrition, no increase in hypothalamic cytokine levels, markers of astrocytes or microglia, or inflammatory signaling pathways were observed. At PND 50, no effect of neonatal overnutriton was found in either sex, whereas at PND 150, males again weighed significantly more than their controls, and this was coincident with an increase in markers of inflammation and astrogliosis in the hypothalamus. Circulating triglycerides and free fatty acids were also elevated in these males, but not in females or in either sex at PND 10. Thus, the effects of fatty acids and estrogens on astrocytes in vitro were analyzed. Our results indicate that changes in circulating fatty acid levels may be involved in the induction of hypothalamic inflammation/gliosis in excess weight gain, even on a normal diet, and that estrogens could participate in the protection of females from these processes. In conclusion, the interaction of developmental influences, dietary composition, age, and sex determines the central inflammatory response and the associated long-term outcomes of excess weight gain.


Metabolomics ◽  
2021 ◽  
Vol 17 (6) ◽  
Author(s):  
Claudia Ottka ◽  
Corinna Weber ◽  
Elisabeth Müller ◽  
Hannes Lohi

Abstract Introduction Phenobarbital is a commonly used anticonvulsant for the treatment of canine epileptic seizures. In addition to its central nervous system (CNS) depressing effects, long-term phenobarbital administration affects liver function. However, broader metabolic consequences of phenobarbital treatment are poorly characterized. Objectives To identify metabolic changes in the sera of phenobarbital-treated dogs and to investigate the relationship between serum phenobarbital concentration and metabolite levels. Methods Leftovers of clinical samples were used: 58 cases with phenobarbital concentrations ranging from 7.8 µg/mL to 50.8 µg/mL, and 25 controls. The study design was cross-sectional. The samples were analyzed by a canine-specific 1H NMR metabolomics platform. Differences between the case and control groups were evaluated by logistic regression. The linear relationship between metabolite and phenobarbital concentrations was evaluated using linear regression. Results Increasing concentrations of glycoprotein acetyls, LDL particle size, palmitic acid, and saturated fatty acids, and decreasing concentrations of albumin, glutamine, histidine, LDL particle concentration, multiple HDL measures, and polyunsaturated fatty acids increased the odds of the sample belonging to the phenobarbital-treated group, having a p-value < .0033, and area under the curve (AUC) > .7. Albumin and glycoprotein acetyls had the best discriminative ability between the groups (AUC: .94). No linear associations between phenobarbital and metabolite concentrations were observed. Conclusion The identified metabolites are known to associate with, for example, liver and CNS function, inflammatory processes and drug binding. The lack of a linear association to phenobarbital concentration suggests that other factors than the blood phenobarbital concentration contribute to the magnitude of metabolic changes.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1049-1049
Author(s):  
Hyojung Kim ◽  
Evelyn Enrione ◽  
Vijaya Narayanan ◽  
Tan Li ◽  
Adriana Campa

Abstract Objectives Previous evidence suggests that vitamin B6 deficiency may have a deleterious impact on aging and the metabolism of polyunsaturated fatty acids (PUFA). However, the relationship of aging with vitamin B6 status and PUFA metabolism is poorly understood; population-based studies to assess the relationship between plasma pyridoxal 5′-phosphate (PLP; an active form of vitamin B6) and PUFA status for older adults are lacking. Thus, we examined the associations between plasma PLP concentration and plasma PUFA concentrations and ratios [eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA] among US older adults. We further investigated the association of adequate (PLP ≥ 20 nmol/L) versus deficient (PLP &lt; 20 nmol/L) vitamin B6 status in those participants with plasma PUFA concentration above the median. Methods A cross-sectional study analyzed 467 participants aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) 2003−2004. Nutrient intake data were estimated from two 24-h recalls and from questionnaires on the use of supplements. Plasma PLP and PUFA concentrations were measured. We used multivariable linear regression for obtaining unstandardized (b) and standardized (β) coefficients; multivariable logistic regression for adjusted odds ratios. Covariates included demographic, socioeconomic, dietary variables, physical activity, smoking, alcohol consumption, prescription medication use, and BMI. Results Plasma PLP was directly associated with plasma EPA (β = 0.176, b = 0.101, P = 0.002), DHA (β = 0.109, b = 0.046, P = 0.004), EPA + DHA (β = 0.137, b = 0.060, P = 0.002), EPA/AA (β = 0.169, b = 0.089, P = 0.009). The odds of having plasma EPA/AA and (EPA + DHA)/AA concentration above the median were greater in those with adequate vitamin B6 compared with those who were deficient [adjusted OR (aOR): 1.32, 95% CI: 0.8−2.17, P = 0.0001; aOR: 2.08, 95% CI: 1.0−4.33, P = 0.049, respectively]. Conclusions In US older adults, plasma PLP was directly associated with plasma EPA, DHA, EPA + DHA, EPA/AA. Adequate vitamin B6 status was associated with having above the median EPA/AA and (EPA + DHA)/AA. These findings suggest that adequate B6 status may positively influence PUFA metabolism in the older US population. Funding Sources No funding sources.


2021 ◽  
Vol 8 ◽  
Author(s):  
Mark G. Filipovic ◽  
Martin F. Reiner ◽  
Saskia Rittirsch ◽  
Irina Irincheeva ◽  
Stefanie Aeschbacher ◽  
...  

Background: Omega-3 fatty acids are associated with a lower risk of cardiovascular disease (CVD) and with beneficial effects on CV risk factors. The albumin-creatinine ratio (ACR) is a risk factor for CVD, all-cause mortality and accelerated glomerular filtration rate (GFR) decline in the general population. We aimed to investigate the association between n-3 PUFAS and ACR in heathy individuals with preserved GFR.Design and Methods: The present cross-sectional analysis is part of the GAPP study, a population-based cohort of healthy adults aged 25–41 years. Individuals with known CVD, diabetes, or a BMI &gt;35 kg/m2 were excluded. eGFR was calculated according to the combined Creatinine/Cystatin C CKD-EPI formula. ACR was obtained from a fasting morning urine sample. The Omega-3 Index (relative amount of EPA and DHA of total fatty acids in %) was obtained from whole blood aliquots.Results: Overall, 2001 participants (median age 37 years IQR 31; 40, 53% female) were included in this analysis. Median Omega-3 Index was 4.59 (IQR 4.06; 5.25) and median eGFR 111 ml/min/1.73 m2 (IQR 103; 118). Median ACR was 0.14 mg/mmol (IQR 0; 0.43). We found a significant inverse association of the Omega-3 Index with ACR (ratio 0.84, 95%CI 0.73–0.96; p = 0.011) which remained after comprehensive adjustment (ratio 0.86, 95%CI 0.74–1.00; p = 0.048). No association of the Omega-3 Index with eGFR was found. The adjusted difference in eGFR per 1-unit increase in Omega3-Index was −0.21 (95%CI −0.76; 0.35; p = 0.47).Conclusions: A higher Omega-3 Index was significantly associated with lower ACR in this young and healthy population with preserved eGFR. Omega-3 fatty acids may exhibit cardio- and nephroprotective effects in healthy individuals through modulation of ACR.


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