Dataset Information

Determinants of the urinary and serum metabolome in children from six European populations.

ABSTRACT:

Background

Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment-health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project ( http://www.projecthelix.eu ).

Methods

Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6-11) recruited from birth cohorts in six European countries were measured using high-throughput ¹H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit).

Results

We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythreonic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r?>?0.18) between urine and serum.

Conclusions

We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children.

SUBMITTER: Lau CE

PROVIDER: S-EPMC6223046 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Determinants of the urinary and serum metabolome in children from six European populations.

Lau Chung-Ho E CE Siskos Alexandros P AP Maitre Léa L Robinson Oliver O Athersuch Toby J TJ Want Elizabeth J EJ Urquiza Jose J Casas Maribel M Vafeiadi Marina M Roumeliotaki Theano T McEachan Rosemary R C RRC Azad Rafaq R Haug Line S LS Meltzer Helle M HM Andrusaityte Sandra S Petraviciene Inga I Grazuleviciene Regina R Thomsen Cathrine C Wright John J Slama Remy R Chatzi Leda L Vrijheid Martine M Keun Hector C HC Coen Muireann M

BMC medicine 20181108 1

<h4>Background</h4>Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment-health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI a ...[more]

PMID: 30404627

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Project description:Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08x10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases.

Project description:BackgroundReference values of ferritin and transferrin for European children do not exist.ObjectiveWe aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3-15-y-old children based on cohort data and to investigate determinants of iron status.MethodsA total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data.ResultsThe age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 μg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: β = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: β = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 μg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)].ConclusionsAge-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3-15 y and may be used in clinical practice.

Dataset Information

Determinants of the urinary and serum metabolome in children from six European populations.

Background

Methods

Results

Conclusions

Publications

Determinants of the urinary and serum metabolome in children from six European populations.

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