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Population epidemiology and concordance for plasma amino acids and precursors in 11-12-year-old children and their parents.

ABSTRACT: Amino acid (AA) concentrations are influenced by both exogenous (e.g. diet, lifestyle) and endogenous factors (e.g. genetic, transcriptomic, epigenetic, and metabolomic). Fasting plasma AA profiles in adulthood are predictive of diabetes risk over periods of up to 12 years. Data on AA profiles in cross-generational cohorts, including individuals from shared gene-environment settings are scarce, but would allow the identification of the contribution of heritable and environmental factors characterising the levels of circulating AAs. This study aimed to investigate parent-child (familial dyad) concordance, absolute differences between generations- (children versus adults), age- (in adults: 28-71 years), and sex-dependent differences in plasma AA concentrations. Plasma AA concentrations were measured by UHPLC/MS-MS in 1166 children [mean (SD) age 11 (0.5) years, 51% female] and 1324 of their parents [44 (5.1) years, 87% female]. AA concentrations were variably concordant between parents and their children (5-41% of variability explained). Most AA concentrations were higher in adults than children, except for the non-essential AAs arginine, aspartic acid, glutamine, hydroxy-proline, proline, and serine. Male adults and children typically had higher AA concentrations than females. The exceptions were alanine, glutamine, glycine, hydroxy-proline, serine, and threonine in girls; and glycine and serine in women. Age, sex, and shared familial factors are important determinants of plasma AA concentrations.

SUBMITTER: Andraos S

PROVIDER: S-EPMC7878730 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Population epidemiology and concordance for plasma amino acids and precursors in 11-12-year-old children and their parents.

Andraos Stephanie S Lange Katherine K Clifford Susan A SA Jones Beatrix B Thorstensen Eric B EB Wake Melissa M Burgner David P DP Saffery Richard R O'Sullivan Justin M JM

Scientific reports 20210211 1

Amino acid (AA) concentrations are influenced by both exogenous (e.g. diet, lifestyle) and endogenous factors (e.g. genetic, transcriptomic, epigenetic, and metabolomic). Fasting plasma AA profiles in adulthood are predictive of diabetes risk over periods of up to 12 years. Data on AA profiles in cross-generational cohorts, including individuals from shared gene-environment settings are scarce, but would allow the identification of the contribution of heritable and environmental factors characte ...[more]

PMID: 33574360

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Project description:BackgroundTrimethylamine N-oxide (TMAO) is a microbiome- and diet-derived metabolite implicated in adverse cardiovascular outcomes. To date, studies of plasma TMAO concentrations have largely focused on individuals with metabolic disease. As such, data on TMAO concentrations in population settings and parent-child dyads are lacking.ObjectivesThis study aimed to investigate parent-child concordance, age, and sex effects on plasma concentrations of TMAO and its precursors [l-carnitine, choline, betaine, and dimethylglycine (DMG)]. Associations between concentrations of TMAO and its precursors and self-reported dietary intakes of animal protein (i.e., red meat, meat products, chicken, fish, milk products, and cheese) and fast-food meals were also investigated.MethodsA total of 1166 children (mean ± SD age: 11 ± 0.5 y, 51% female) and 1324 parents (mean ± SD age: 44 ± 5.1 y, 87% female) had a biomedical assessment as part of Growing Up in Australia's Child Health Checkpoint. Plasma TMAO and precursor concentrations were quantified using ultra-high-pressure LC coupled with tandem MS.ResultsFamilial dyads significantly contributed to plasma TMAO and precursor concentrations (P < 0.0001), explaining 37% of variance for TMAO concentrations. Least-square mean ± SE plasma TMAO was lower in children (0.79 ± 0.02 µM on the log-scale) than in adults (1.22 ± 0.02 µM). By contrast, children's betaine (40.30 ± 0.34 µM) and DMG concentrations (1.02 ± 0.01 µM on the log-scale) were higher than adults' betaine (37.50 ± 0.32 µM) and DMG concentrations (0.80 ± 0.01 µM) (P < 0.0001). Mean values of all metabolites, except adult TMAO, were higher in males than in females (P < 0.001). Greater reported intake of red meat and fish was associated with higher TMAO concentrations in both children [estimates (95% CIs) for red meat: 0.06 (0.01, 0.10); fish: 0.11 (0.06, 0.17)] and adults [red meat: 0.13 (0.08, 0.17); meat products: 0.07 (0.03, 0.12); and fish: 0.09 (0.04, 0.14)].ConclusionsAge, sex, and shared family factors, including diet, contribute to variation in plasma concentrations of TMAO and its precursors.

Project description:OBJECTIVES:To describe the distribution of albuminuria among Australian children aged 11-12 years and their parents, and assess its intergenerational concordance within parent-child dyads. DESIGN:Population-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children. SETTING:Assessment centres (seven Australian cities and eight regional towns) and home visits across Australia, February 2015 to March 2016. PARTICIPANTS:Of all participating CheckPoint families (n=1874), 1557 children (46.2% girls) and 1454 parents (85.5% mothers) provided random urine samples at the visit; samples from menstruating females were excluded. OUTCOME MEASURES:Urine albumin-to-creatinine ratio (ACR) and its components (urine albumin and creatinine concentration); albuminuria was defined as an ACR ≥3.4 mg/mmol. Pearson's correlation coefficients and multivariable linear regression models assessed parent-child concordance, using log-transformed data due to skewing. Survey weights and methods were applied to account for the complex sample design. RESULTS:The median ACR for children was 1.03 mg/mmol (IQR 0.65-1.97) and 1.01 mg/mmol (IQR 0.60-2.09) for adults. The median ACR was higher in girls (1.20, IQR 0.71-2.65) than boys (0.90, IQR 0.61-1.65) and in mothers (1.13, IQR 0.63-2.33) than fathers (0.66, IQR 0.41-1.05). Albuminuria was detected in 15.1% of children (girls 20.8%, boys 10.1%) and 13.5% of adults (15.1% mothers, 4.0% fathers) had albuminuria. There was a small correlation between parent and child ACR (Pearson correlation coefficient 0.06, 95% CI 0.01 to 0.12). CONCLUSIONS:Albuminuria is common among Australian children and adults, which is of concern because it predicts risk for kidney and cardiovascular disease, and mortality. The weak concordance among intergenerational pairs for urine ACR suggests either that genetic heritability is low or that it becomes evident only at later offspring life stages.

Project description:OBJECTIVES:To describe objectively measured sleep characteristics in children aged 11-12 years and in parents and to examine intergenerational concordance of sleep characteristics. DESIGN:Population-based cross-sectional study (the Child Health CheckPoint), nested within the Longitudinal Study of Australian Children. SETTING:Data were collected between February 2015 and March 2016 across assessment centres in Australian major cities and selected regional towns. PARTICIPANTS:Of the participating CheckPoint families (n=1874), sleep data were available for 1261 children (mean age 12 years, 50% girls), 1358 parents (mean age 43.8 years; 88% mothers) and 1077 biological parent-child pairs. Survey weights were applied and statistical methods accounted for the complex sample design, stratification and clustering within postcodes. OUTCOME MEASURES:Parents and children were asked to wear a GENEActive wrist-worn accelerometer for 8 days to collect objective sleep data. Primary outcomes were average sleep duration, onset, offset, day-to-day variability and efficiency. All sleep characteristics were weighted 5:2 to account for weekdays versus weekends. Biological parent-child concordance was quantified using Pearson's correlation coefficients in unadjusted models and regression coefficients in adjusted models. RESULTS:The mean sleep duration of parents and children was 501 min (SD 56) and 565 min (SD 44), respectively; the mean sleep onset was 22:42 and 22:02, the mean sleep offset was 07:07 and 07:27, efficiency was 85.4% and 84.1%, and day-to-day variability was 9.9% and 7.4%, respectively. Parent-child correlation for sleep duration was 0.22 (95% CI 0.10 to 0.28), sleep onset was 0.42 (0.19 to 0.46), sleep offset was 0.58 (0.49 to 0.64), day-to-day variability was 0.25 (0.09 to 0.34) and sleep efficiency was 0.23 (0.10 to 0.27). CONCLUSIONS:These normative values for objective sleep characteristics suggest that, while most parents and children show adequate sleep duration, poor-quality (low efficiency) sleep is common. Parent-child concordance was strongest for sleep onset/offset, most likely reflecting shared environments, and modest for duration, variability and efficiency.

Project description:OBJECTIVES:Nuclear 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. DESIGN:The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. SETTING:Blood samples collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns; February 2015-March 2016. PARTICIPANTS:1180 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 MEASURES:228 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. RESULTS:We 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. CONCLUSIONS:We 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.

Project description:OBJECTIVES:To describe a well-established marker of cardiovascular risk, carotid intima-media thickness (IMT) and related measures (artery distensibility and elasticity) in children aged 11-12 years old and mid-life adults, and examine associations within parent-child dyads. DESIGN:Cross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC). SETTING:Assessment centres in seven Australian major cities and eight selected regional towns, February 2015 to March 2016. PARTICIPANTS:Of all participating CheckPoint families (n=1874), 1489 children (50.0% girls) and 1476 parents (86.8% mothers) with carotid IMT data were included. Survey weights and methods were applied to account for LSAC's complex sample design and clustering within postcodes and strata. OUTCOME MEASURES:Ultrasound of the right carotid artery was performed using standardised protocols. Primary outcomes were mean and maximum far-wall carotid IMT, quantified using semiautomated edge detection software. Secondary outcomes were carotid artery distensibility and elasticity. Pearson's correlation coefficients and multivariable linear regression models were used to assess parent-child concordance. Random effects modelling on a subset of ultrasounds (with repeated measurements) was used to assess reliability of the child carotid IMT measure. RESULTS:The average mean and maximum child carotid IMT were 0.50 mm (SD 0.06) and 0.58 mm (SD 0.05), respectively. In adults, average mean and maximum carotid IMT were 0.57 mm (SD 0.07) and 0.66 mm (SD 0.10), respectively. Mother-child correlations for mean and maximum carotid IMT were 0.12 (95% CI 0.05 to 0.23) and 0.10 (95% CI 0.03 to 0.21), respectively. For carotid artery distensibility and elasticity, mother-child correlations were 0.19 (95% CI 0.10 to 0.25) and 0.11 (95% CI 0.02 to 0.18), respectively. There was no strong evidence of father-child correlation in any measure. CONCLUSIONS:We provide Australian values for carotid vascular measures and report a modest mother-child concordance. Both genetic and environmental exposures are likely to contribute to carotid IMT.

Project description:OBJECTIVES:To describe distributions and concordance of retinal microvasculature measurements in a population-based sample of Australian parent-child dyads at child age 11-12 years. DESIGN:Cross-sectional Child Health CheckPoint study, between waves 6 and 7 of the national population-based Longitudinal Study of Australian Children (LSAC). SETTING:Assessment centres in seven Australian cities, February 2015-March 2016. PARTICIPANTS:Of 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 MEASURES:Retinal 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. RESULTS:Mean (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. CONCLUSIONS:Arteriolar 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.

Project description:OBJECTIVES:To describe the epidemiology of lung function in Australian children aged 11-12 years and their parents, and explore the degree of intergenerational concordance. DESIGN:Cross-sectional study (the Child Health CheckPoint) nested in the Longitudinal Study of Australian Children (LSAC). SETTING:Assessment centres in seven Australian cities and eight regional towns, February 2015 to March 2016. Families unable to attend a clinic appointment were offered a home visit during the same period. PARTICIPANTS:1874 families (53% of all eligible) participated in the study. Lung function data were available for 1759 children aged 11-12 years and 1774 parents (1668 biological pairs). OUTCOME MEASURES:Participants completed spirometry with measures including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and mid expiratory flow (MEF), converted to z-scores using Global Lung Initiative equations. Parent-child concordance was assessed using Pearson's correlation coefficients and multivariable linear regression models. Survey weights and methods accounted for LSAC's complex sampling, stratification and clustering within postcodes. RESULTS:All lung function measures followed approximately normal distributions. Mean (SD) for FEV1, FVC and MEF z-scores in children were 0.33 (1.07), 0.83 (1.14) and -0.48 (1.09), respectively. Mean (SD) in parents were 0.28 (1.10), 0.85 (1.15) and -0.45 (1.10), respectively. Parent FEV1, FVC and MEF were associated with child lung function with significant positive correlation coefficients (0.22, 95% CI 0.17 to 0.26; 0.24, 95% CI 0.20 to 0.29; and 0.24, 95% CI 0.20 to 0.29, respectively). CONCLUSIONS:Mean lung volumes were larger but with smaller airway size than international standards for both parents and children in this population sample. Modest associations between parent and child lung function highlight the potential for better identification of 'at risk' populations. Therefore, these findings may aid the development of health policy that aims to prevent the onset or limit the progression of lung disease.

Project description:OBJECTIVES:Overweight and obesity remain at historically high levels, cluster within families and are established risk factors for multiple diseases. We describe the epidemiology and cross-generational concordance of body composition among Australian children aged 11-12 years and their parents. DESIGN:The population-based cross-sectional Child Health CheckPoint study, nested within the Longitudinal Study of Australian Children (LSAC). SETTING:Assessment centres in seven major Australian cities and eight regional cities, or home visits; February 2015-March 2016. PARTICIPANTS:Of all participating CheckPoint families (n=1874), body composition data were available for 1872 children (49% girls) and 1852 parents (mean age 43.7 years; 88% mothers), including 1830 biological parent-child pairs. MEASURES:Height, weight, body mass index (BMI), waist circumference and waist-to-height ratio for all participants; body fat and fat-free mass by four-limb bioimpedence analysis (BIA) at assessment centres, or body fat percentage by two-limb BIA at home visits. Analysis: parent-child concordance was assessed using (i) Pearson's correlation coefficients, and (ii) partial correlation coefficients adjusted for age, sex and socioeconomic disadvantage. Survey weights and methods accounted for LSAC's complex sample design. RESULTS:20.7% of children were overweight and 6.2% obese, as were 33.5% and 31.6% of parents. Boys and girls showed similar distributions for all body composition measures but, despite similar BMI and waist-to-height ratio, mothers had higher proportions of total and truncal fat than fathers. Parent-child partial correlations were greatest for height (0.37, 95% CI 0.33 to 0.42). Other anthropometric and fat/lean measures showed strikingly similar partial correlations, ranging from 0.25 (95% CI 0.20 to 0.29) for waist circumference to 0.30 (95% CI 0.25 to 0.34) for fat-free percentage. Whole-sample and sex-specific percentile values are provided for all measures. CONCLUSIONS:Excess adiposity remains prevalent in Australian children and parents. Moderate cross-generational concordance across all measures of leanness and adiposity is already evident by late childhood.

Project description:OBJECTIVES:To describe the epidemiology and parent-child concordance of vascular function in a population-based sample of Australian parent-child dyads at child age 11-12 years. DESIGN:Cross-sectional study (Child Health CheckPoint), nested within a prospective cohort study, the Longitudinal Study of Australian Children (LSAC). SETTING:Assessment centres in seven major Australian cities and eight regional towns or home visits, February 2015-March 2016. PARTICIPANTS:Of all participating CheckPoint families (n=1874), 1840 children (49% girls) and 1802 parents (88% mothers) provided vascular function data. Survey weights and methods were applied to account for LSAC's complex sample design and clustering within postcodes and strata. OUTCOME MEASURES:The SphygmoCor XCEL assessed vascular function, generating estimates of brachial and central systolic blood pressure and diastolic blood pressure, central pulse pressure, augmentation index and carotid-femoral pulse wave velocity. Pearson's correlation coefficients and multivariable linear regression models estimated parent-child concordance. RESULTS:Hypertension was present in 3.9% of children and 9.0% of parents. Mean child and parent values for augmentation index were 4.5% (SD 11.6) and 21.3% (SD 12.3), respectively, and those for carotid-femoral pulse wave velocity were 4.48 m/s (SD 0.59) and 6.85 m/s (SD 1.14), respectively. Parent-child correlation for brachial systolic blood pressure was 0.20 (95% CI 0.15 to 0.24), brachial diastolic blood pressure 0.21 (95% CI 0.16 to 0.26), central systolic blood pressure 0.21 (95% CI 0.16 to 0.25), central diastolic blood pressure 0.21 (95% CI0.17 to 0.26), central pulse pressure 0.19 (95% CI 0.14 to 0.24), augmentation index 0.28 (95% CI 0.23 to 0.32) and pulse wave velocity 0.22 (95% CI 0.18 to 0.27). CONCLUSIONS:We report Australian values for traditional and more novel vascular function markers, providing a reference for future population studies. Cross-generational concordance in multiple vascular function markers is already established by age 11-12 years, with mechanisms of heritability remaining to be explored.

Dataset Information

Population epidemiology and concordance for plasma amino acids and precursors in 11-12-year-old children and their parents.

Publications

Population epidemiology and concordance for plasma amino acids and precursors in 11-12-year-old children and their parents.

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